Colon cancer initiating cells (CCICs) are more tumorigenic and metastatic than the majority of colorectal cancer (CRC) cells. CCICs have also been associated with stem cell-like properties. However, there is a lack of system-level understanding of what mechanisms distinguish CCICs from common CRC cells. We compared the transcriptomes of CD133+ CCICs and CD133− CRC cells from multiple sources, which identified a distinct metabolic signature for CD133high CCICs. High-resolution unbiased metabolomics was then performed to validate this CCIC metabolic signature. Specifically, levels of enzymes and metabolites involved in glycolysis, the citric acid (TCA) cycle, and cysteine and methionine metabolism are altered in CCICs. Analyses of the alterations further suggest an epigenetic link. This metabolic signature provides mechanistic insights into CCIC phenotypes and may serve as potential biomarkers and therapeutic targets for future CRC treatment.
In this paper, three-dimensional finite element analysis using the commercial ANSYS software is performed to study the thermal performance of a thermally enhanced FC-PBGA (flip-chip plastic ball grid array) assembly in both natural and forced convection environments. The thermally enhanced FC-PBGA assembly is a basic FC-PBGA assembly with a lid attached on top, after which an extruded-fin heatsink is attached on the top of the lid. The finite element model is complete enough to include key elements such as bumps, solder balls, substrate, printed circuit board, extruded-fin heatsink, lid, vias, TIM1 (thermal interface material 1), TIM2 (thermal interface material 2), lid-substrate adhesive and ground planes for both signal and power. Temperature fields are simulated and presented for several package configurations. Thermal resistance is calculated to characterize and compare the thermal performance by considering alternative design parameters of the polymer-based materials and the thermal enhancement components. The polymer-based materials include underfill, TIM1, TIM2, lid-substrate adhesive and substrate core material. The specific thermal enhancement components are the extruded-fin heatsink and the lid.
Extensive understanding and management of the thermal-mechanical characteristics of novel packaging designs during the bonding process are indispensable to the realization of the technologies. Thus, this paper attempts to explore the bonding process-induced thermal-mechanical behaviors of an advanced flip chip (FC) electronic packaging. FC packaging employs a novel anisotropic conductive film, which is a thin composite film composed of polymer matrix and thousands of millions of highly oriented, 1-D silver (Ag) nanowires on the scale of 200 nanometers in diameter. For carrying out the process simulation, a process-dependent finite element (FE) simulation methodology that integrates both thermal and nonlinear contact FE analyses and a special meshing scheme is applied. The material properties of the nanoscale Ag wires are first explored using molecular dynamics (MD) simulations. By the characterized material properties of the Ag nanowires, the effective material properties of the composite film are derived through two theoretical approaches: 1) the rule-of-mixture (ROM) technique and 2) the proposed FE method-based approach. The predicted results by these two approaches are extensively compared with each other to examine the feasibility of using the widely used ROM technique for such cases. In addition, the validity of the proposed process-dependent FE simulation methodology is also confirmed through three experiments: 1) micro-thermocouple measurement of temperature; 2) Twyman-Green Moiré Interferometry measurement of out-of-plane deformations; and 3) Portable Engineering Moiré Interferometry measurement of in-plane deformations. Throughout the investigation, the effectiveness of the novel interconnect technology is demonstrated. Good agreement with the experiments is also obtained. It is found that the technology may ensure good electrical performance and structural integrity, not only at room temperature but even at elevated temperature, based on its substantial contact stresses but minor peeling stresses on the bonding line, together with a moderate, process-induced warpage on the substrate.Index Terms-Anisotropic conductive film, finite-element (FE) modeling, flip-chip (FC) technology, Moiré interferometry measurement, molecular dynamics (MD) simulations, template assisted nanowire growth technique.
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