Cancer cell invasion is a major component of metastasis and is responsible for extensive cell diffusion into and major destruction of tissues. Cells exhibit complex invasion modes, including a variety of collective behaviors. This phenomenon results in the structural heterogeneity of the extracellular matrix (ECM) in tissues. Here, we systematically investigated the environmental heterogeneity facilitating tumor cell invasion via a combination of in vitro cell migration experiments and computer simulations. Specifically, we constructed an ECM microenvironment in a microfabricated biochip and successfully created a three-dimensional (3D) funnel-like matrigel interface inside. Scanning electron microscopy demonstrated that the interface was at the interior defects of the nano-scale molecular anisotropic orientation and the localized structural density variations in the matrigel. Our results, particularly the correlation of the collective migration pattern with the geometric features of the funnel-like interface, indicate that this heterogeneous in vitro ECM structure strongly guides and promotes aggressive cell invasion in the rigid matrigel space. A cellular automaton model was proposed based on our experimental observations, and the associated quantitative analysis indicated that cell invasion was initiated and controlled by several mechanisms, including microenvironment heterogeneity, long-range cell-cell homotype and gradient-driven directional cellular migration. Our work shows the feasibility of constructing a complex and heterogeneous in vitro 3D ECM microenvironment that mimics the in vivo environment. Moreover, our results indicate that ECM heterogeneity is essential in controlling collective cell invasive behaviors and therefore determining metastasis efficiency.
Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the “switch” from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent “switch” behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural “competition” between the tumor and tumor suppression factors in the microenvironment. This competition either results in a “stalemate” for a period of time in which the tumor either eventually wins (spontaneously emerges) or is eradicated; or it leads to a situation in which the tumor is eradicated before such a “stalemate” could ever develop. We also predict that if the number of actively dividing cells within the proliferative rim of the tumor reaches a critical, yet low level, the dormant tumor has a high probability to resume rapid growth. Our findings may shed light on the fundamental understanding of cancer dormancy.
Maximally random jammed (MRJ) particle packings can be viewed as prototypical glasses in that they are maximally disordered while simultaneously being mechanically rigid. The prediction of the MRJ packing density ϕMRJ, among other packing properties of frictionless particles, still poses many theoretical challenges, even for congruent spheres or disks. Using the geometric-structure approach, we derive for the first time a highly accurate formula for MRJ densities for a very wide class of two-dimensional frictionless packings, namely, binary convex superdisks, with shapes that continuously interpolate between circles and squares. By incorporating specific attributes of MRJ states and a novel organizing principle, our formula yields predictions of ϕMRJ that are in excellent agreement with corresponding computer-simulation estimates in almost the entire α-x plane with semi-axis ratio α and small-particle relative number concentration x. Importantly, in the monodisperse circle limit, the predicted ϕMRJ = 0.834 agrees very well with the very recently numerically discovered MRJ density of 0.827, which distinguishes it from high-density “random-close packing” polycrystalline states and hence provides a stringent test on the theory. Similarly, for non-circular monodisperse superdisks, we predict MRJ states with densities that are appreciably smaller than is conventionally thought to be achievable by standard packing protocols.
In this study, Sn grain orientation and Cu6Sn5 IMC fraction, size, and morphology are characterized in 3D, in pure Sn based solder joints. The obtained results show differences in morphology of Sn grains and IMC precipitates as a function of location within the solder joint indicating influence of local cooling rate differences. Ex situ and in situ electromigration tests done on 250 um and 500 um pure Sn solder joints elucidate the evolution of microstructure, specifically Sn grain growth, IMC segregation and surface degradation. This research implements 3D quantification of microstructural features over micro and nano-scales, thereby enabling a multi-scale / multi-characterization approach.
To test the above proposition, I conduct the empirical analysis in three steps. In the first step, I investigate foreign banks’ management model by surveying 13 major foreign banks locally incorporated in Mainland China. The results suggest that these 13 foreign banks can be categorized into three distinct groups based on their management model: intergrators, customer-followers, and parent-followers. The results also indicate that intergrators have the highest level of localization while parent-followers have the lowest level of localization.
In the second step, I conduct DEA (Data Envelope Analysis) and CAMEL (Capital Adequacy, Asset Quality, Management, Earnings, Liquidity Analysis) to assess the operating efficiency of these 13 foreign banks. The assessment is conducted in two ways: 1) the inter-group comparison between foreign banks and local Chinese banks; 2) the intra-group comparison between the three distinct groups of foreign banks identified in the first step. The results indicates that the principal factor driving the operating efficiency of both local Chinese banks and foreign banks is the comprehensive technical efficiency, which includes both the quality of management and the quality of technical elements. I also find the uptrend of technical efficiency of the integrators is more stable than that of the other two groups of foreign banks.
Finally, I integrate the results from step one and step two to assess the relevance between foreign banks’ localization level and operating efficiency. I find that foreign banks that score higher in localization tend to have a higher level of operating efficiency. Although this finding is not conclusive about the causal relationship between localization and operating efficiency, it nevertheless suggests that the management model of the higher performing integrators can serve as references for the other foreign banks attempting to enhance their localization and operating efficiency. I also discuss the future trends of development in the banking industry in China and what foreign banks can learn from local Chinese banks to improve their market positions.
The scope of this project is a combination of material science engineering and mechanical engineering. Overall, the main goal of this project is to develop a lightweight concrete that maintains its original strength profile. Initial research has shown that a plastic-concrete composite could create a more lightweight concrete than that made using the typical gravel aggregate for concrete, while still maintaining the physical strength that concrete is known for. This will be accomplished by varying the amount of plastic in the aggregate. If successful, this project would allow concrete to be used in applications it would typically not be suitable for.<br/>After testing the strength of the concrete specimens with varying fills of plastic aggregate it was determined that the control group experienced an average peak stress of 2089 psi, the 16.67% plastic group experienced an average peak stress of 2649 psi, the 33.3% plastic group experienced an average peak stress of 1852 psi, and the 50% plastic group experienced an average stress of 924.5 psi. The average time to reach the peak stress was found to be 12 minutes and 24 seconds in the control group, 15 minutes and 34 seconds in the 16.7% plastic group, 9 minutes and 45 seconds in the 33.3% plastic group, and 10 minutes and 58 seconds in the 50% plastic group. Taking the average of the normalized weights of the cylindrical samples it was determined that the control group weighed 14.773 oz/in, the 16.7% plastic group weighed 15 oz/in, the 33.3% plastic group weighed 14.573 oz/in, and the 50% plastic group weighed 12.959 oz/in. Based on these results it can be concluded that a small addition of plastic aggregate can be beneficial in creating a lighter, stronger concrete. The results show that a 16.7% fill ratio of plastic to rock aggregate can increase the failure time and the peak strength of a composite concrete. Overall, the experiment was successful in analyzing the effects of recycled plastic aggregate in composite concrete. <br/>Some possible future studies related to this subject material are adding aluminum to the concrete, having better molds, looking for the right consistency in each mixture, mixing for each mold individually, and performing other tests on the samples.
The scope of this project is a combination of material science engineering and<br/>mechanical engineering. Overall, the main goal of this project is to develop a lightweight<br/>concrete that maintains its original strength profile. Initial research has shown that a<br/>plastic-concrete composite could create a more lightweight concrete than that made using the<br/>typical gravel aggregate for concrete, while still maintaining the physical strength that concrete is<br/>known for. This will be accomplished by varying the amount of plastic in the aggregate. If<br/>successful, this project would allow concrete to be used in applications it would typically not be<br/>suitable for.<br/>After testing the strength of the concrete specimens with varying fills of plastic aggregate<br/>it was determined that the control group experienced an average peak stress of 2089 psi, the<br/>16.67% plastic group experienced an average peak stress of 2649 psi, the 33.3% plastic group<br/>experienced an average peak stress of 1852 psi, and the 50% plastic group experienced an<br/>average stress of 924.5 psi. The average time to reach the peak stress was found to be 12 minutes<br/>and 24 seconds in the control group, 15 minutes and 34 seconds in the 16.7% plastic group, 9<br/>minutes and 45 seconds in the 33.3% plastic group, and 10 minutes and 58 seconds in the 50%<br/>plastic group. Taking the average of the normalized weights of the cylindrical samples it was<br/>determined that the control group weighed 14.773 oz/in, the 16.7% plastic group weighed 15<br/>oz/in, the 33.3% plastic group weighed 14.573 oz/in, and the 50% plastic group weighed 12.959<br/>oz/in. Based on these results it can be concluded that a small addition of plastic aggregate can be<br/>beneficial in creating a lighter, stronger concrete. The results show that a 16.7% fill ratio of<br/>plastic to rock aggregate can increase the failure time and the peak strength of a composite<br/>concrete. Overall, the experiment was successful in analyzing the effects of recycled plastic<br/>aggregate in composite concrete.<br/>Some possible future studies related to this subject material are adding aluminum to the<br/>concrete, having better molds, looking for the right consistency in each mixture, mixing for each<br/>mold individually, and performing other tests on the samples.
