This review summarizes the recent advances on the application of ^(57)Fe Mössbauer spectrometry to study the magnetic and phase characteristics of Nd–Fe–B-based permanent magnets. First of all, the hyperfine st...This review summarizes the recent advances on the application of ^(57)Fe Mössbauer spectrometry to study the magnetic and phase characteristics of Nd–Fe–B-based permanent magnets. First of all, the hyperfine structures of the Ce_(2)Fe_(14)B,(Ce,Nd)_(2)Fe_(14)B and MM_(2)Fe_(14)B phases are well-defined by using the model based on the Wigner-Seitz analysis of the crystal structure. The results show that the isomer shift δ and the quadrupole splitting öEQ of those 2:14:1 phases show minor changes with the Nd content, while the hyperfine field Bhfincreases monotonically with increasing Nd content and its value is influenced by the element segregation and phase separation in the 2:14:1 phase. Then, the hyperfine structures of the low fraction secondary phases are determined by the ^(57)Fe Mössbauer spectrometry due to its high sensitivity. On this basis,the content, magnetic behavior, and magnetization of the REFe_(2) phase, the amorphous grain boundary(GB) phase, and the amorphous worm-like phase, as well as their effects on the magnetic properties, are systematically studied.展开更多
^57Fe Mossbauer spectroscopic study was carried out on the organic rich sedimentary samples collected at different depth intervals from newly drilled test well Chinnewala Tibba-1（CT-1） located in Jaisalmer Petrolife...^57Fe Mossbauer spectroscopic study was carried out on the organic rich sedimentary samples collected at different depth intervals from newly drilled test well Chinnewala Tibba-1（CT-1） located in Jaisalmer Petroliferous basin India. It is found that iron is mainly distributed in high spin Fe^3＋and Fe^2＋ state in clay minerals. The plot of Fe^2＋/（Fe^2＋＋ Fe^3＋） indicates the presence of poor redox conditions in the samples.Results obtained are also compared with those already reported in the literature. This comparison shows that there may exist a correlation between prospecting of the basin, the redox environment in sediments and the nature of iron bearing minerals distributed in the sedimentary sequence.展开更多
Using conversion electron spectroscopy(CEMS) and slow positron beam, the chemical state of 57Fe(100keV,3×1016 cm-2) implanted into ZrO2 containing 0.03 mole fraction Y2O3(ZY3) and its thermodynamic behavior duri...Using conversion electron spectroscopy(CEMS) and slow positron beam, the chemical state of 57Fe(100keV,3×1016 cm-2) implanted into ZrO2 containing 0.03 mole fraction Y2O3(ZY3) and its thermodynamic behavior during annealing process at 200 ￣ 500℃ are studied.For as-implanted sample, Fe chemical states of Fe0,Fe2+ and Fe3+ are observed,and assigned to the superparamagnetic metallic iron cluster,iron dimer(and trimer) and complex of the Fe3+ associated with canon vacancy (V) and oxygens respectively.After annealing at 400℃ the complexes of Fe3+-V are mostly dissolved,and the prior phase to α-Fe and α-Fe nano-crystalline cluster are present in the sample.Meanwhile the mixed conducting of oxygen-ions and electrons in the ZY3 sample containing Fe appears,it may correlate with the different iron charge states and their relative amounts,in particular with the α-Fe nano-granule.展开更多
MEK1/2 inhibitors are clinically approved for the treatment of BRAF-mutant melanoma,where they are used in combination with BRAF inhibitors,and are undergoing evaluation in other malignancies.Acquired resistance to ME...MEK1/2 inhibitors are clinically approved for the treatment of BRAF-mutant melanoma,where they are used in combination with BRAF inhibitors,and are undergoing evaluation in other malignancies.Acquired resistance to MEK1/2 inhibitors,including selumetinib(AZD6244/ARRY-142866),can arise through amplification of BRAF^(V600E) or KRAS^(G13D) to reinstate ERK1/2 signalling.We have found that BRAF^(V600E) amplification and selumetinib resistance are fully reversible following drug withdrawal.This is because resistant cells with BRAF^(V600E) amplification become addicted to selumetinib to maintain a precise level of ERK1/2 signalling(2%-3%of total ERK1/2 active),that is optimal for cell proliferation and survival.Selumetinib withdrawal drives ERK1/2 activation outside of this critical“sweet spot”(~20%-30%of ERK1/2 active)resulting in a p57^(KIP2)-dependent G1 cell cycle arrest and senescence or expression of NOXA and cell death with features of autophagy;these terminal responses select against cells with amplified BRAF^(V600E).ERK1/2-dependent p57^(KIP2) expression is required for loss of BRAF^(V600E) amplification and determines the rate of reversal of selumetinib resistance.Growth of selumetinib-resistant cells with BRAF^(V600E) amplification as tumour xenografts also requires the presence of selumetinib to“clamp”ERK1/2 activity within the sweet spot.Thus,BRAF^(V600E) amplification confers a selective disadvantage or“fitness deficit”during drug withdrawal,providing a rationale for intermittent dosing to forestall resistance.Remarkably,selumetinib resistance driven by KRAS^(G13D) amplification/upregulation is not reversible.In these cells ERK1/2 reactivation does not inhibit proliferation but drives a ZEB1-dependent epithelial-to-mesenchymal transition that increases cell motility and promotes resistance to traditional chemotherapy agents.Our results reveal that the emergence of drug-addicted,MEKi-resistant cells,and the opportunity this may afford for intermittent dosing schedules(“drug holidays”),may be determined by the nature of the amplified driving oncogene(BRAF^(V600E) vs.KRAS^(G13D)),further exemplifying the difficulties of targeting KRAS mutant tumour cells.展开更多
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(Grant Nos.LY20E010002,LR18E010001,and LD19E010001)the National Natural Science Foundation of China(Grant Nos.U1704253 and 51801047)+2 种基金Liaoning Revitalization Talents Program(Grant No.XLYC1807177)the Key Research and Development plan of Zhejiang Province,China(Grant No.2020C05014)Ten Thousand Talents Plan of Zhejiang Province,China(Grant No.2018R52003)。
文摘This review summarizes the recent advances on the application of ^(57)Fe Mössbauer spectrometry to study the magnetic and phase characteristics of Nd–Fe–B-based permanent magnets. First of all, the hyperfine structures of the Ce_(2)Fe_(14)B,(Ce,Nd)_(2)Fe_(14)B and MM_(2)Fe_(14)B phases are well-defined by using the model based on the Wigner-Seitz analysis of the crystal structure. The results show that the isomer shift δ and the quadrupole splitting öEQ of those 2:14:1 phases show minor changes with the Nd content, while the hyperfine field Bhfincreases monotonically with increasing Nd content and its value is influenced by the element segregation and phase separation in the 2:14:1 phase. Then, the hyperfine structures of the low fraction secondary phases are determined by the ^(57)Fe Mössbauer spectrometry due to its high sensitivity. On this basis,the content, magnetic behavior, and magnetization of the REFe_(2) phase, the amorphous grain boundary(GB) phase, and the amorphous worm-like phase, as well as their effects on the magnetic properties, are systematically studied.
文摘^57Fe Mossbauer spectroscopic study was carried out on the organic rich sedimentary samples collected at different depth intervals from newly drilled test well Chinnewala Tibba-1（CT-1） located in Jaisalmer Petroliferous basin India. It is found that iron is mainly distributed in high spin Fe^3＋and Fe^2＋ state in clay minerals. The plot of Fe^2＋/（Fe^2＋＋ Fe^3＋） indicates the presence of poor redox conditions in the samples.Results obtained are also compared with those already reported in the literature. This comparison shows that there may exist a correlation between prospecting of the basin, the redox environment in sediments and the nature of iron bearing minerals distributed in the sedimentary sequence.
文摘Using conversion electron spectroscopy(CEMS) and slow positron beam, the chemical state of 57Fe(100keV,3×1016 cm-2) implanted into ZrO2 containing 0.03 mole fraction Y2O3(ZY3) and its thermodynamic behavior during annealing process at 200 ￣ 500℃ are studied.For as-implanted sample, Fe chemical states of Fe0,Fe2+ and Fe3+ are observed,and assigned to the superparamagnetic metallic iron cluster,iron dimer(and trimer) and complex of the Fe3+ associated with canon vacancy (V) and oxygens respectively.After annealing at 400℃ the complexes of Fe3+-V are mostly dissolved,and the prior phase to α-Fe and α-Fe nano-crystalline cluster are present in the sample.Meanwhile the mixed conducting of oxygen-ions and electrons in the ZY3 sample containing Fe appears,it may correlate with the different iron charge states and their relative amounts,in particular with the α-Fe nano-granule.
基金Work in the Cook laboratory relevant to this article was supported by Cancer Research UK A14867,a Cambridge Cancer Centre PhD Studentship,a BBSRC PhD studentship,to Sale MJ and Cook SJan AstraZeneca-Cambridge Cancer Centre Collaborative Award,to Sale MJ and Cook SJInstitute Strategic Programme(BB/J004456/1,BB/P013384/1)from BBSRC to Balmanno K and Cook SJ,and AstraZeneca.
文摘MEK1/2 inhibitors are clinically approved for the treatment of BRAF-mutant melanoma,where they are used in combination with BRAF inhibitors,and are undergoing evaluation in other malignancies.Acquired resistance to MEK1/2 inhibitors,including selumetinib(AZD6244/ARRY-142866),can arise through amplification of BRAF^(V600E) or KRAS^(G13D) to reinstate ERK1/2 signalling.We have found that BRAF^(V600E) amplification and selumetinib resistance are fully reversible following drug withdrawal.This is because resistant cells with BRAF^(V600E) amplification become addicted to selumetinib to maintain a precise level of ERK1/2 signalling(2%-3%of total ERK1/2 active),that is optimal for cell proliferation and survival.Selumetinib withdrawal drives ERK1/2 activation outside of this critical“sweet spot”(~20%-30%of ERK1/2 active)resulting in a p57^(KIP2)-dependent G1 cell cycle arrest and senescence or expression of NOXA and cell death with features of autophagy;these terminal responses select against cells with amplified BRAF^(V600E).ERK1/2-dependent p57^(KIP2) expression is required for loss of BRAF^(V600E) amplification and determines the rate of reversal of selumetinib resistance.Growth of selumetinib-resistant cells with BRAF^(V600E) amplification as tumour xenografts also requires the presence of selumetinib to“clamp”ERK1/2 activity within the sweet spot.Thus,BRAF^(V600E) amplification confers a selective disadvantage or“fitness deficit”during drug withdrawal,providing a rationale for intermittent dosing to forestall resistance.Remarkably,selumetinib resistance driven by KRAS^(G13D) amplification/upregulation is not reversible.In these cells ERK1/2 reactivation does not inhibit proliferation but drives a ZEB1-dependent epithelial-to-mesenchymal transition that increases cell motility and promotes resistance to traditional chemotherapy agents.Our results reveal that the emergence of drug-addicted,MEKi-resistant cells,and the opportunity this may afford for intermittent dosing schedules(“drug holidays”),may be determined by the nature of the amplified driving oncogene(BRAF^(V600E) vs.KRAS^(G13D)),further exemplifying the difficulties of targeting KRAS mutant tumour cells.
