Phosphatidylinositol 3-kinase/Akt signaling pathway and angiogenesis

Angiogenesis, the formation of new blood vessels from preexisting ones, is tightly controlled under physiological conditions, and deregulated angiogenesis contributes to many pathological situations. This study investigates the role of PI3K/Akt pathway in both physiological and pathological angiogenesis. Angiopoietin-1 (Ang1) is an endothelial specific growth factor that plays a critical role in vessel maturation and stabilization during angiogenesis. We found that Ang1 potently induced p70S6K1 activation in human umbilical vein endothelial cells (HUVECs). p70S6K1 is a downstream target of PI3K, but its role in angiogenesis has not be defined. In the work shown in Chapter 2, p70S6K1 activity in HUVECs was modified by adenovirus-mediated gene transfer, and we provided first evidence that p70S6K1 is directly involved in Ang1-induced angiogenic endothelial responses, including cell migration, invasion, survival, and capillary morphogenesis. We also examined the effect and mechanisms of action of insulin-like growth factor-I (IGF-I) on the expression of cyclooxygenase-2 (COX-2), which is a crucial player in angiogenesis and tumorigenesis. In Chapter 3, we showed that IGF-I efficiently upregulated COX-2 expression in human ovarian cancer cells, which was differentially regulated by PI3K, MAPK, and PKC signaling pathways at transcriptional and/or post-transcriptional levels. In the study shown in Chapter 4, we selectively modulated PI3K/Akt signaling in either human microvascular endothelial cells or cancer cells, and examined the effects on tumor angiogenesis using a chimeric tumor model. We found that PI3K and Akt activities in both endothelial cells and tumor cells contributed to tumor growth and angiogenesis, suggesting that targeting PI3K/Akt signaling in both cellular compartments may be more effective for anti-cancer therapy. In Chapter 5, we demonstrated that resveratrol has a strong inhibitory effects on hypoxiainducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells. The effects are associated with suppression of PI3K/Akt and MAPK pathways, interference with protein translational machinery, and enhancement of HIF-1alpha protein degradation through the proteasome. This work provides a better understanding of the molecular basis of angiogenesis, which we hope may facilitate the identification of novel therapeutic targets in the future

Is collective financing feasible for small and micro-sized enterprises? An evolutionary game analysis of the credit market in China

With regards to the evolutionary game model of collective financing between commercial banks and small and medium-sized enterprises (SMEs), the self-guarantee mechanism formed within the enterprise group is taken as the research background in the paper. Under the circumstances of mortgage assets and unsecured assets, the changing trend of the strategies of both sides in the process of collective financing is made a discussion respectively. Followed by the evolutionary game, it is concluded that under the stable management strategy, commercial banks will offer different loan strategies (collective or separate) after comprehensively judging the repayment probability of enterprises. For SMEs, loans at a reasonable rate can prompt them to pay them back on time, how- ever, high loan costs can lead to the possibility of total financing default and the adverse circumstances of risk diffusion. More importantly, collective financing of unsecured assets does not increase the bank’s credit risk, while not only can it help banks reduce the cost of loan review, but also alleviate the problem of information opacity in SMEs, prevent the occurrence of default risk and reduce the threshold for enterprises to obtain funds and also provide a new way to solve the financing problems of SMEs

The Strategy Integration of Network Marketing for the Tourism Enterprises in Shaanxi Province

With the development of modern science and information technology, the Internet has brought about the new opportunity for the development of tourism enterprises, and also made network marketing possible. Starting form concrete situation of tourism industry in Shaanxi Province and making a breakthrough in traditional marketing strategies province, this paper suggests the strategy integration of network marketing for the tourism enterprise in Shaanxi Provinc

Leveraging RRAM to Design Efficient Digital Circuits and Systems for Beyond Von Neumann in-Memory Computing

Due to the physical separation of their processing elements and storage units, contemporary digital computers are confronted with the thorny memory-wall problem. The strategy of in-memory computing has been considered as a promising solution to overcome the von Neumann bottleneck and design high-performance, energy-efficient computing systems. Moreover, in the post Moore era, post-CMOS technologies have received intense interests for possible future digital logic applications beyond the CMOS scaling limits. Motivated by these perspectives from system level to device level, this thesis proposes two effective processing-in-memory schemes to construct the non-von Neumann systems based on nonvolatile resistive random-access memory (RRAM). In the first scheme, we present functionally complete stateful logic gates based on a CMOS-compatible 2-transistor-2-RRAM (2T2R) structure. In this structure, the programmable logic functionality is determined by the amplitude of operation voltages, rather than its circuit topology. A reconfigurable 3T2R chain with programmable interconnects is used to implement complex combinational logic circuits. The design has a highly regular and symmetric circuit structure, making it easy for design, integration, and fabrication, while the operations are flexible yet clean. Easily integrated as 3-dimensional (3-D) stacked arrays, two proposed memory architectures not only serve as regular 3-D memory arrays but also perform in-memory-computing within the same layer and between the stacked layers. The second scheme leverages hybrid logic in the same hardware to design efficient digital circuits and systems with low computational complexity. Multiple-bit ripple-carry adder (RCA), pipelined RCA, and prefix tree adder are shown as example circuits, using the same regular chain structure, to validate the design efficiency. The design principles, computational complexity, and performance are discussed and compared to the CMOS technology and other state-of-the-art post-CMOS implementations. The overall evaluation shows superior performance in speed and area. The result of the study could build a technology cell library that can be potentially used as input to a technology-mapping algorithm. The proposed hybrid-logic methodology presents prospect of hardware acceleration and future beyond-von Neumann in-memory computing architectures

Model for Dynamic Multiple of CPPI Strategy

Focusing on the parameter “Multiple” of CPPI strategy, this study proposes a dynamic setting model of multiple for gap risk management purpose. First, CPPI gap risk is measured as the probability that the value loss of active asset exceeds its allowed maximum drop determined by a given multiple setting. Moreover, according to the statistical estimation using SV-EVT approach, a dynamic choice of multiple is detailed as a function of time-varying asset volatility, expected loss, and the possibility of occurrence of extreme events in the active asset returns illustrated empirically on Shanghai composite index data. This study not only enriches the literature of dynamic proportion portfolio insurance, but also provides a practical reference for CPPI investors to choose a moderate risky exposure achieving gap risk management, which promotes CPPI’s application in emerging capital market