Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

/pdf/cancer-genome-landscapes-qmge4i5y2h.pdf

Cancer Genome Landscapes

Interest in the topic of tumour metabolism has waxed and waned over the past century of cancer research. The early observations of Warburg and his contemporaries established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. However, the initial hypotheses that were based on these observations proved inadequate to explain tumorigenesis, and the oncogene revolution pushed tumour metabolism to the margins of cancer research. In recent years, interest has been renewed as it has become clear that many of the signalling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism, making this topic once again one of the most intense areas of research in cancer biology.

/pdf/regulation-of-cancer-cell-metabolism-1dhy51t2fl.pdf

Regulation of cancer cell metabolism

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.

/pdf/cancer-associated-idh1-mutations-produce-2-hydroxyglutarate-3hnshr7hh1.pdf

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

This paper is devoted to the output feedback control for a class of nonlinear systems with unknown backlash-like hysteresis at the input. Based on a high-gain observer, an adaptive dynamic surface control scheme is proposed which is able to mitigate the effect of the hysteresis, to eliminate the explosion of terms inherent in backstepping control, and in particular, by introducing an initialization technique, to guarantee the ∞ performance of the system's tracking error. Another advantage of the proposed scheme is that the adaptive law is needed only at the first design step, which greatly simplifies the design procedure and makes our control easy to implement.



Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society

An adaptive output feedback dynamic surface control for a class of nonlinear systems with unknown backlash-like hysteresis

Summary

We investigate the problem of robust adaptive tracking by output feedback for a class of uncertain nonlinear systems. Based on the high-gain scaling technique and a new adaptive law, a linear-like output feedback controller is constructed. Only one dynamic gain is designed, which makes the controller easier to implement. Furthermore, by modifying the update law, the adaptive controller is robust to bounded external disturbance and is able to guarantee the convergence of the output tracking error to an arbitrarily small residual set. A numerical example is used to illustrate the effectiveness of the proposed method. Copyright © 2015 John Wiley & Sons, Ltd.

Robust adaptive tracking of uncertain nonlinear systems by output feedback

There has been extensive interest in developing a highly efficient production route toward graphene oxide (GO). Although the conventional chemical oxidation is widely used to synthesize GO, it suff...

Recent advances in green, safe, and fast production of graphene oxide via electrochemical approaches

In this note, we address the problem of global output feedback tracking for a class of low-triangular nonlinear systems. Instead of using backstepping approach, we propose a novel dynamic gain scaling technique to design the output feedback controller. With a change of coordinates, a linear-like controller is constructed, which avoids the repeated derivatives of the nonlinearities depending on the observer states and the dynamic gain in backstepping approach and therefore, greatly simplifies the design procedure. It is proved that by using the new technique, global stability of the closed loop system can be guaranteed and the output tracking error converges to zero exponentially.

A New Approach to Global Asymptotic Tracking for a Class of Low-Triangular Nonlinear Systems via Output Feedback

This paper aims at exploring an adaptive fuzzy dynamic surface control (DSC) with prespecified tracking performance for a class of nonlinear systems in strict-feedback form Incorporating DSC technique into fuzzy logic systems (FLSs), it is shown that the design procedure and the computational burden can be greatly reduced Moreover, by introducing a performance function in controller design, the prespecified tracking performance, ie the convergence rate, the allowed maximum overshoot and the steady state error, can be achieved Simulation results are presented to demonstrate the efficiency of the proposed scheme



Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society

Yan Lin

Papers

An adaptive output feedback dynamic surface control for a class of nonlinear systems with unknown backlash-like hysteresis

Robust adaptive tracking of uncertain nonlinear systems by output feedback

Recent advances in green, safe, and fast production of graphene oxide via electrochemical approaches

A New Approach to Global Asymptotic Tracking for a Class of Low-Triangular Nonlinear Systems via Output Feedback

Adaptive fuzzy dynamic surface control with prespecified tracking performance for a class of nonlinear systems