The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best-investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow-tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a welldefined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML).

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Recognition of pathogen‐associated molecular signatures is critically important in proper activation of the immune system. The toll‐like receptor (TLR) signaling network is responsible for innate immune response. In mammalians, there are 11 TLRs that recognize a variety of ligands from pathogens to trigger immunological responses. In this paper, we present a comprehensive map of TLRs and interleukin 1 receptor signaling networks based on papers published so far. The map illustrates the possible existence of a main network subsystem that has a bow‐tie structure in which myeloid differentiation primary response gene 88 (MyD88) is a nonredundant core element, two collateral subsystems with small GTPase and phosphatidylinositol signaling, and MyD88‐independent pathway. There is extensive crosstalk between the main bow‐tie network and subsystems, as well as feedback and feedforward controls. One obvious feature of this network is the fragility against removal of the nonredundant core element, which is MyD88, and involvement of collateral subsystems for generating different reactions and gene expressions for different stimuli.

The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases.

Mossbauer spectra of Fe-8.0 at.%C, Fe-10.9 at.%Al-8.2 at.%C, Fe-1.4 at.%Mn-7.9 at.%C, Fe-2.4 at.%Mn-7.8 at%C and Fe-14.6 at.%Ni-6.2 at.%C FCC gamma -irons have been measured in order to investigate the distribution and the local interactions of C in the lattice. The local interaction energies in nearest and second-nearest C-C and M-C (M: Al, Mn, Ni) atomic pairs have been determined by a Monte Carlo method simulating the distribution obtained. The interaction energies in nearest and second-nearest C-C pairs are strongly repulsive, in contrast to the weak interaction in second-nearest N-N pairs. The results are compared with the interaction energies derived from activity data. The interaction in nearest Al-C pairs is repulsive but that in second-nearest pairs is strongly attractive, which can lead to the formation of the perovskite Fe3AlC-type ordering. The interaction between nearest Mn and C atoms is strongly attractive, while between Ni and C the interaction is very weak.

The metabolic syndrome is a highly complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension. Type 2 diabetes is a major manifestation of this syndrome, although increased risk for cardiovascular disease (CVD) often precedes the onset of frank clinical diabetes. Prevention and cure for this disease constellation is of major importance to world health. Because the metabolic syndrome affects multiple interacting organ systems (i.e., it is a systemic disease), a systems-level analysis of disease evolution is essential for both complete elucidation of its pathophysiology and improved approaches to therapy. The goal of this review is to provide a perspective on systems-level approaches to metabolic syndrome, with particular emphasis on type 2 diabetes. We consider that metabolic syndromes take over inherent dynamics of our body that ensure robustness against unstable food supply and pathogenic infections, and lead to chronic inflammation that ultimately results in CVD. This exemplifies how trade-offs between robustness against common perturbations (unstable food and infections) and fragility against unusual perturbations (high-energy content foods and low-energy utilization lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches that target fragility of emergent robustness of the disease state have been discussed. A detailed molecular interaction map for adipocyte, hepatocyte, skeletal muscle cell, and pancreatic ␤-cell cross-talk in the metabolic syndrome can be viewed at http://www.systems-biology.org/001/ 003.html. Diabetes 53 (Suppl. 3)

A Mossbauer effect measurement of 57Fe has been performed for the Fe-N austenite in order to study the interaction between nitrogen atoms and the distribution among the octahedral sites of the FCC lattice. The spectrum for Fe-N austenite is decomposed into one singlet gamma 0 and two sets of doublets gamma 1 and gamma 2 which are identified as being caused by iron atoms with different configurations of nitrogen atoms at the nearest-neighbour sites. The fractional intensities for the three components are precisely determined by taking into account the effect of the absorber thickness. It is concluded from the analysis that the interaction between the first-nearest-neighbour nitrogen atoms is strongly repulsive and that between the second nearest nitrogen is weakly attractive.

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