Loss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth.

Oesophageal cancer is an aggressive tumour which responds poorly to both chemotherapy and radiation therapy and has a poor prognosis. Thus, a greater understanding of the biology of oesophageal cancer is needed in order to identify novel therapeutic targets. Among these targets p38 MAPK isoforms are becoming increasingly important for a variety of cellular functions. The physiological functions of p38α and -β are now well documented in contrast to -γ and -δ which are comparatively under-studied and ill-defined. A major obstacle to deciphering the role(s) of the latter two p38 isoforms is the lack of specific chemical activators and inhibitors. In this study, we analysed p38 MAPK isoform expression in oesophageal cancer cell lines as well as human normal and tumour tissue. We observed specifically differential p38δ expression. The role(s) of p38δ and active (phosphorylated) p38δ (p-p38δ) in oesophageal squamous cell carcinoma (OESCC) was delineated using wild-type p38δ as well as active p-p38δ, generated by fusing p38δ to its upstream activator MKK6b(E) via a decapeptide (Gly-Glu)5 linker. OESCC cell lines which are p38δ-negative (KE-3 and -8) grew more quickly than cell lines (KE-6 and -10) which express endogenous p38δ. Re-introduction of p38δ resulted in a time-dependent decrease in OESCC cell proliferation which was exacerbated with p-p38δ. In addition, we observed that p38δ and p-p38δ negatively regulated OESCC cell migration in vitro. Finally both p38δ and p-p38δ altered OESCC anchorage-independent growth. Our results suggest that p38δ and p-p38δ have a role in the suppression of OESCC. Our research may provide a new potential target for the treatment of oesophageal cancer.

Average-case analysis of power consumption in embedded systems

Power efficiency is one of the most important constraints in the design of embedded systems since such systems are generally driven by batteries with limited energy budget or restricted power supply. In every embedded system, there are one or more processor cores to run the software and interact with the other hardware components of the system. The power consumption of the processor core(s) has an important impact on the total power dissipated in the system. Hence, the processor power optimization is crucial in satisfying the power consumption constraints, and developing low-power embedded systems. A key aspect of research in processor power optimization and management is “power estimation”. Having a fast and accurate method for processor power estimation at design time helps the designer to explore a large space of design possibilities, to make the optimal choices for developing a power efficient processor. Likewise, understanding the processor power dissipation behaviour of a specific software/application is the key for choosing appropriate algorithms in order to write power efficient software. Simulation-based methods for measuring the processor power achieve very high accuracy, but are available only late in the design process, and are often quite slow. Therefore, the need has arisen for faster, higher-level power prediction methods that allow the system designer to explore many alternatives for developing powerefficient hardware and software. The aim of this thesis is to present fast and high-level power models for the prediction of processor power consumption. Power predictability in this work is achieved in two ways: first, using a design method to develop power predictable circuits; second, analysing the power of the functions in the code which repeat during execution, then building the power model based on average number of repetitions. In the first case, a design method called Asynchronous Charge Sharing Logic (ACSL) is used to implement the Arithmetic Logic Unit (ALU) for the 8051 microcontroller. The ACSL circuits are power predictable due to the independency of their power consumption to the input data. Based on this property, a fast prediction method is presented to estimate the power of ALU by analysing the software program, and extracting the number of ALU-related instructions. This method achieves less than 1% error in power estimation and more than 100 times speedup in comparison to conventional simulation-based methods. In the second case, an average-case processor energy model is developed for the Insertion sort algorithm based on the number of comparisons that take place in the execution of the algorithm. The average number of comparisons is calculated using a high level methodology called MOdular Quantitative Analysis (MOQA). The parameters of the energy model are measured for the LEON3 processor core, but the model is general and can be used for any processor. The model has been validated through the power measurement experiments, and offers high accuracy and orders of magnitude speedup over the simulation-based method.

Person, community, Tian: the emergence of order and harmony in Chinese philosophy

This thesis clarifies how the concept of tian functions in Chinese thought, and what tianren heyi (the continuity between tian and humans) means in the Chinese context. With a new interpretation about tianren heyi, I provide a new contribution for understanding these Chinese concepts for an English speaking audience. Tian is not a fixed concept like the idea of heaven, rather, it can be the principle for one’s immanent world. The meaning of the term changes depending on the context it is being used in, and can also be neutral when necessary. Continuity means that there is a resonance and reciprocity in the way these aspects of cosmology emerge together. Humans and tian are not being unified or connected—there is simply continuity between them. What happens is that a productive relationship between them produces depth, harmony, and enhanced significance. Through the interaction between humanity and tian, the human world gains order, and from the perspective of tian, gains harmony. This different understanding the continuity between humanity and tian leads to a new understanding of timing or the appropriateness in li. In the process of practice and self cultivation, it is seen that li is also an idea that is not fixed to one single interpretation as it is connected with timing and appropriateness. The Classical Chinese concept of “Person” (ren 人), as the concrete context of li, is the centre of this practice. Because of the unfixed natures of tian and li, one needs to be flexible in order to cater to their demands. This embodies the freedom of the subject in Chinese thought. As the outcome of li, the social and political structure is shaped in this process, the examples being the models of “great union” and “small tranquillity” (Chapter 3) in Chinese tradition.