Alzheimer’s disease(AD)is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology.Brain imaging biomarker genomics has been developed in rec...Alzheimer’s disease(AD)is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology.Brain imaging biomarker genomics has been developed in recent years to reveal potential AD pathological mechanisms and provide early diagnoses.This technique integrates multimodal imaging phenotypes with genetic data in a noninvasive and high-throughput manner.In this review,we summarize the basic analytical framework of brain imaging biomarker genomics and elucidate two main implementation scenarios of this technique in AD studies:(1)exploring novel biomarkers and seeking mutual interpretability and(2)providing a diagnosis and prognosis for AD with combined use of machine learning methods and brain imaging biomarker genomics.Importantly,we highlight the necessity of brain imaging biomarker genomics,discuss the strengths and limitations of current methods,and propose directions for development of this research field.展开更多
With the drastic reduction of the TSV diameter leading to a critical dimension comparable to the Cu-filled grain size,the grain condition strongly influences the thermo-mechanical behavior of the TSV.In this work,the ...With the drastic reduction of the TSV diameter leading to a critical dimension comparable to the Cu-filled grain size,the grain condition strongly influences the thermo-mechanical behavior of the TSV.In this work,the TSV-Cu cross-section with different grain sizes is characterized by EBSD,confirming that the sidewall grain size(0.638–1.580μm)is smaller compared to other regions(1.022–2.134μm).A finite element model(FEM)considering copper grains is constructed by using Voronoi diagrams to investigate the effect of sidewall grain size as well as area on the thermo-mechanical behavior during annealing.The material parameters in the FEM are optimized through nanoindentation inversion and considering the mechanical property anisotropy of copper grains.The yield strengthσy and hardening exponent n of TSV-Cu are 74.6 MPa and 0.514.The simulation results indicate that the protrusion of TSV-Cu after annealing tends to increase initially and then decrease with smaller sidewall grain size and area.The maximum increase in protrusion caused by the two variables can reach 6.74%and 14.6%,respectively,relative to the average grain condition.Additionally,the simulation results were validated by quantifying grain boundaries in TSV-Cu samples with varying grain sizes.展开更多
基金the National Natural Science Foundation of China(82020108013)Science and Technology Innovation 2030 Major Projects(2022ZD0211600).
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology.Brain imaging biomarker genomics has been developed in recent years to reveal potential AD pathological mechanisms and provide early diagnoses.This technique integrates multimodal imaging phenotypes with genetic data in a noninvasive and high-throughput manner.In this review,we summarize the basic analytical framework of brain imaging biomarker genomics and elucidate two main implementation scenarios of this technique in AD studies:(1)exploring novel biomarkers and seeking mutual interpretability and(2)providing a diagnosis and prognosis for AD with combined use of machine learning methods and brain imaging biomarker genomics.Importantly,we highlight the necessity of brain imaging biomarker genomics,discuss the strengths and limitations of current methods,and propose directions for development of this research field.
基金supported by the Major Program(JD)of Hubei Province(No.2023BAA008)the National Key R&D Program of China(No.2022YFB3207100)+1 种基金the Hubei Provincial Strategic Scientist Training Plan(No.2022EJD009)the Fundamental Research Funds for the Central Universities(No.2042023kf1041).
文摘With the drastic reduction of the TSV diameter leading to a critical dimension comparable to the Cu-filled grain size,the grain condition strongly influences the thermo-mechanical behavior of the TSV.In this work,the TSV-Cu cross-section with different grain sizes is characterized by EBSD,confirming that the sidewall grain size(0.638–1.580μm)is smaller compared to other regions(1.022–2.134μm).A finite element model(FEM)considering copper grains is constructed by using Voronoi diagrams to investigate the effect of sidewall grain size as well as area on the thermo-mechanical behavior during annealing.The material parameters in the FEM are optimized through nanoindentation inversion and considering the mechanical property anisotropy of copper grains.The yield strengthσy and hardening exponent n of TSV-Cu are 74.6 MPa and 0.514.The simulation results indicate that the protrusion of TSV-Cu after annealing tends to increase initially and then decrease with smaller sidewall grain size and area.The maximum increase in protrusion caused by the two variables can reach 6.74%and 14.6%,respectively,relative to the average grain condition.Additionally,the simulation results were validated by quantifying grain boundaries in TSV-Cu samples with varying grain sizes.
