The present work optimizes the groove size in the friction stir welding (FSW) of 6061-T6 aluminium alloy (AA) with Al
2
O
3
powder particle reinforcement. Here the four cases are considered for the ...groove depth of 1 mm, 1.5 mm, 2 mm and 3 mm, and the groove width is 1 mm (for all cases) on each AA6061-T6 workpiece material. The COMSOL Multiphysics software was used to model the temperature rise during friction stir welding. In the experimental analysis, the optical micrograph (OM) and scanning electron microscope (SEM) analysis of the weld samples revealed that the powder particle agglomerate near the stir zone region and the Al
2
O
3
powder are not homogeneously mixed with the aluminium matrix when the depth is too large. The maximum tensile strength and hardness were recorded on the weld samples when the groove depth was 2 mm.
Graphical abstract
Breast cancer (BC) is a heterogeneous disease that is the most common cancer in women worldwide. However, precise subtyping and corresponding treatments have improved patient outcomes. Hormone ...receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative (HR+/HER2-) BC with BRCA1 and/or BRCA2 mutations (BRCA1/2m) is a unique BC subset with dual drivers: homologous recombination deficiency and hormone receptor signaling. Wild-type BRCA1/2 suppresses estrogen receptor-mediated signaling. Loss-of-function mutations in
BRCA1
/2 release estrogen receptor suppression, leading to reduced sensitivity to endocrine therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) exert antitumor effects against this subtype and can be used in combination with endocrine therapy. Although PARPis have been evaluated in metastatic triple-negative breast cancer, their efficacy against HR+/HER2- BC has not been clearly established. The present review summarizes recent advances and prospects in the progress of the HR+/HER2-/BRCA1/2m subgroup. As such, this article provides theoretical guidance for future research and promotes the use of PARPis for the treatment of HR+/HER2-/BRCA1/2m BC.
In the current study, the friction stir additive manufacturing (FSAM) technique was used to fabricate a three-layered build by using 3 mm thick sheets of AA5083 (top and bottom layer) and AA7075-T6 ...(middle layer) alloys. The effect of microstructure and texture evolution on the mechanical properties was studied comprehensively by using optical microscopy (OM), field emission scanning electron microscopy (FESEM), electron backscattered diffraction (EBSD), Vickers microhardness, and miniature tensile tests. Stir zones (SZ) along the build depth consist of fine equiaxed grains with complete intermixing of materials. The top and bottom region of the build shows appreciable strength and microhardness in comparison to BM (AA5083). The precipitate dissolution due to the multiple thermal cycles is the main contributing factor to decreased strength and microhardness in the middle region of the build. Microstructure gradients are observed owing to varying degrees of temperature gradient along the build depth. Texture analysis reveals the presence of ideal shear texture components A
1
*/A
2*,
B/B̅, and C in the stir zones of the fabricated build, which suggests the presence of sufficient heat input during processing. The orientation distribution function (ODF) signifies the presence of recrystallization texture (Cube, P, and Goss) and plain strain texture (Brass and S) components in the SZ.
Critical control of the welding conditions produced a fine ferrite–martensite duplex structure with the martensite volume fraction of around 33% in friction stir welding (FSW) of medium carbon ...(0.45wt% C) low alloy steel sheets. This microstructure provides the preferable combination of tensile strength and ductility. The findings were achieved to clarify the effect of the welding speed on the weldability. The fraction of low angle grain boundaries (LAGBs) decrease with increasing welding speed. At the welding speed of 400mm/min, the top region microstructure consists of lath martensite, while the bottom region shows a fine ferrite–pearlite structure. This microstructural variation can be linked with the distribution of the peak temperatures along the thickness of the weld. Additionally, it was shown that a non-contact thermal imaging system can be used as an effective tool for the online monitoring of several kinds of weld decays.
The development of the microstructure and mechanical properties during friction stir welding of 6063-T4 aluminium alloy was investigated through electron backscatter diffraction (EBSD) and ...transmission electron microscopy (TEM) techniques and mechanical testing. Grain boundary and dislocation strengthening were observed to be the dominant strengthening mechanisms occurring in the stir zone (SZ). While the precipitates morphologies were sensitive to the weld zone temperatures, the grain size and grain boundary misorientations were related to strain (
𝜖
), strain rates (
𝜖
̇
), and peak temperatures (
T
p
). Severe gradients in the crystallographic texture were observed at the top and bottom and on the retreating and advancing sides of the weld obtained at 48 mm/min welding speed. The optimal strength and ductility of a transverse tensile specimen were achieved when the cold defects, overaging in heat affected zones (HAZs), and grain size in stir zone (SZ) were minimized. While the yield strength of the longitudinal tensile specimens was controlled by the grain size, dislocation density and fraction of low angle boundaries (LABs), the uniform elongation was controlled by the fraction of high angle boundaries (HABs). In addition, a successful implementation of more simple geometry weld zone finite element model than earlier reported work for use in forming simulations was also proposed.
Estrogens play a critical role in the initiation and progression of breast cancer. Estrogen receptor (ER)α, ERβ, and G protein-coupled estrogen receptor are the primary receptors for estrogen in ...breast cancer. These receptors are mainly activated by binding with estrogens. The crosstalk between ERs and membrane growth factor receptors creates additional pathways that amplify the effects of their ligands and promote tumor growth. This crosstalk may cause endocrine therapy resistance in ERα-positive breast cancer. Furthermore, this may explain the resistance to anti-human epidermal growth factor receptor-2 (HER2) treatment in ERα-/HER2-positive breast cancer and chemotherapy resistance in triple-negative breast cancer. Accordingly, it is necessary to understand the complex crosstalk between ERs and growth factor receptors. In this review, we delineate the crosstalk between ERs and membrane growth factor receptors in breast cancer. Moreover, this review highlights the current progress in clinical treatment and discusses how pharmaceuticals target the crosstalk. Lastly, we discuss the current challenges and propose potential solutions regarding the implications of targeting crosstalk via pharmacological inhibition. Overall, the present review provides a landscape of the crosstalk between ERs and membrane growth factor receptors in breast cancer, along with valuable insights for future studies and clinical treatments using a chemotherapy-sparing regimen to improve patient quality of life.
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•Crosstalk between estrogen receptors and membrane growth factor receptors is crucial in breast cancer development and progression.•Targeting this crosstalk has yielded preliminary preclinical and clinical results; however, further research is essential.•This review discusses crosstalk between estrogen receptors and membrane growth factor receptors in breast cancer.
This work investigates the microstructure, mechanical characteristics, and texture evolution of friction stir welding (FSW) of AA6061-T6 metal matrix composites (MMCs) reinforced with silicon carbide ...(SiC) and zinc (Zn) particles. The SZ region of the SiC and Zn particle-reinforced aluminium matrix (Al-matrix) composites has ultra-fine grain refinements of 4.79 and 4.18 μm, respectively, compared to base metal (BM) particle sizes of 44.97 μm. Ultra-fine grain refinement in the SZ zone produces dynamic recrystallization with particulate-driven nucleation, Zenner Hollomon, and homogeneous SiC/Zn particle distribution in the Al-matrix. Recrystallization texture components P {011} , cube {001} , rotating cube (H) {001} , and F {111} , along with primary shear texture components (B/B¯, and C), suggested DRX at the joint interface in the SiC-reinforced Al-matrix composite. However, the Zn-reinforced Al-matrix composite has a high plain strain, recrystallization, and deformation texture components of copper {112} , Brass {011} , cube {001} , Goss {110}, and P 011 , and major shear texture components (B/B¯ and C). SiC and Zn-reinforced Al-matrix composites have 110 ± 4 and 120 ± 5 HV0.2 average microhardness, respectively. Also, SiC and Zn-reinforced Al-matrix composites have 224 and 236 MPa tensile strengths, respectively.
Joining thick sections of aluminum alloys by friction stir welding (FSW) in a single pass needs to overcome many challenges before it comes to full-scale industrial use. Important parameters ...controlling the structure-properties relationships both across weld cross-section and through thickness direction were investigated through mechanical testing, electron backscatter diffraction technique, transmission electron microscopy, and occurrence of serrated plastic flow. The evolution of the properties in the weld cross-section shows that the presence of undissolved and fragmented Al
6
MnFe particles cause discrepancies in establishing the Hall-Petch relationship, and derive the strengthening from the Orowan strengthening mechanism. A ‘stop action’ friction stir weld has been prepared to understand the role of geometrical features of the tool probe in the development of the final microstructure after complete weld. Sectioning through the ‘stop action’ weld with the probe
in situ
displays the individual effect of thread and flat on the grain structure formation. The material at the thread surface experiences more severe deformation than the material at flat surface. Both the high-angle boundaries and mean grain size are found to be higher at the thread surface. The strain hardening capacity, stress serration amplitude, and frequency are observed to be higher in the stir zone than other weld regions.
A 3D-coupled thermo-mechanical modelling using COMSOL Multiphysics software is used to investigate the effect of the number of flats on the material flow and the local heat generation at the tool pin ...profile/workpiece interface. It has been shown that the optimum number of flats machined from a cylindrical surface tool is four. The larger contact length will offer larger frictional heating area and hence causing the greater amount of the local thermal softening of the workpiece material. The growth of the built-up-edge provides the local disturbance in the material flow causing the additional flow paths and torque. The calculated torque ratio
Δ
M
M
is the highest in the case of four number of flats which is an important indicator of local heat generation. The microstructural evolution close to the flat pin/workpiece interface shows the presence of coarse grain structure along with the higher fraction of high angle boundaries (HABs). Based on the observed microstructural features, it has been confirmed that the resulting microstructural features are greatly affected by the tool flat interface due to the local heat generation and plastic flow.
The microstructure development in the weld key-hole along the plate thickness was investigated through scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and transmission ...electron microscopy (TEM) techniques. A fundamental understanding of the contact condition at the tool/workpiece interface in a Triflat
T
M
designed friction stir welding (FSW) tool is presented. The development of grain structure for “stop-action” weld reveals that the plasticized material undergoes complex interacting flows due to the presence of threads and flats. The localized high material velocities induce a significant increase in the strain rate within thread space and thereby tune the Zener-Hollomon parameter. An interesting analogy is drawn between the evolution of the secondary shear zone (SSZ) in a typical metal cutting and the steady state FSW processes. The presence of different morphology of the material filling the thread space is linked to the local variation of the contact state variables along weld thickness. It was found that the contact state is governed by the intrinsic interface characteristics and the mechanical property of the material. It was also shown that the presence of larger particles (> 0.5
μ
m) is responsible for the formation of high angle boundaries (HAGBs) and random recrystallization texture within the stir zone, reflecting random grain orientation due to particle-stimulated nucleation (PSN).
