The Development and the Use of Experimental Animal Models to Study the Underlying Mechanisms of CA Formation

Cerebral aneurysms (CAs) have a high prevalence and can cause a lethal subarachnoid hemorrhage. Currently, CAs can only be treated with invasive surgical procedures. To unravel the underlying mechanisms of CA formation and to develop new therapeutic drugs for CAs, animal models of CA have been established, modified, and analyzed. Experimental findings from these models have clarified some of the potential mechanisms of CA formation, especially the relationship between hemodynamic stress and chronic inflammation. Increased hemodynamic stress acting at the site of bifurcation of cerebral arteries triggers an inflammatory response mediated by various proinflammatory molecules in arterial walls, inducing pathological changes in the models similar to those observed in the walls of human CAs. Findings from animal studies have provided new insights into CA formation and may contribute to the development of new therapeutic drugs for CAs

The Effect of Dynamical Gauge Field on the Chiral Fermion on a boundary

We study the effect of dynamical gauge field on the Kaplan's chiral fermion on a boundary in the strong gauge coupling limit in the extra dimension. To all orders of the hopping parameter expansion, we prove exact parity invariance of the fermion propagator on the boundary. This means that the chiral property of the boundary fermion, which seems to survive even in the presence of the gauge field from a perturbative point of view, is completely destroyed by the dynamics of the gauge field.Comment: 16 pages (including 7 figures), LaTeX, UT-675, KEK-TH-39

Partial Product Updates for Agents of Detectable Failure and Logical Obstruction to Task Solvability

The logical method proposed by Goubault, Ledent, and Rajsbaum provides a novel way to show the unsolvability of distributed tasks by means of a logical obstruction, which is an epistemic logic formula describing the reason of unsolvability. In this paper, we introduce the notion of partial product update, which refines that of product update in the original logical method, to encompass distributed tasks and protocols modeled by impure simplicial complexes. With this extended notion of partial product update, the original logical method is generalized so that it allows the application of logical obstruction to show unsolvability results in a distributed environment where the failure of agents is detectable. We demonstrate the use of the logical method by giving a concrete logical obstruction and showing that the consensus task is unsolvable by the single-round synchronous message-passing protocol

Fractal Structure in Two-Dimensional Quantum Regge Calculus

We study the fractal structure of the surface in two-dimensional quantum Regge calculus by performing Monte Carlo simulation with up to 200,000 triangles. The result can be compared with the universal scaling function obtained analytically in the continuum limit of dynamical triangulation, which provides us with a definite criterion whether Regge calculus serves as a proper regularization of quantum gravity. When the scale-invariant measure is taken as the measure of the link-length integration, we observe the correct scaling behavior in the data for the type of loop attached to a baby universe. The data seem to converge to the universal scaling function as the number of triangles is increased. The data for the type of loop attached to the mother universe, on the other hand, shows no scaling behavior up to the present size.Comment: 13 pages + 8 figures, LaTeX, UT-683, KEK-TH-401 (double-spacing command removed. sorry.

Critical role of TNF-alpha-TNFR1 signaling in intracranial aneurysm formation

BACKGROUND: Intracranial aneurysm (IA) is a socially important disease due to its high incidence in the general public and the severity of resultant subarachnoid hemorrhage that follows rupture. Despite the social importance of IA as a cause of subarachnoid hemorrhage, there is no medical treatment to prevent rupture, except for surgical procedures, because the mechanisms regulating IA formation are poorly understood. Therefore, these mechanisms should be elucidated to identify a therapeutic target for IA treatment. In human IAs, the presence of inflammatory responses, such as an increase of tumor necrosis factor (TNF)-alpha, have been observed, suggesting a role for inflammation in IA formation. Recent investigations using rodent models of IAs have revealed the crucial role of inflammatory responses in IA formation, supporting the results of human studies. Thus, we identified nuclear factor (NF)-kappaB as a critical mediator of inflammation regulating IA formation, by inducing downstream pro-inflammatory genes such as MCP-1, a chemoattractant for macrophages, and COX-2. In this study, we focused on TNF-alpha signaling as a potential cascade that regulates NF-kappaB-mediated IA formation. RESULTS: We first confirmed an increase in TNF-alpha content in IA walls during IA formation, as expected based on human studies. Consistently, the activity of TNF-alpha converting enzyme (TACE), an enzyme responsible for TNF-alpha release, was induced in the arterial walls after aneurysm induction in a rat model. Next, we subjected tumor necrosis factor receptor superfamily member 1a (TNFR1)-deficient mice to the IA model to clarify the contribution of TNF-alpha-TNFR1 signaling to pathogenesis, and confirmed significant suppression of IA formation in TNFR1-deficient mice. Furthermore, in the IA walls of TNFR1-deficient mice, inflammatory responses, including NF-kappaB activation, subsequent expression of MCP-1 and COX-2, and infiltration of macrophages into the IA lesion, were greatly suppressed compared with those in wild-type mice. CONCLUSIONS: In this study, using rodent models of IAs, we clarified the crucial role of TNF-alpha-TNFR1 signaling in the pathogenesis of IAs by inducing inflammatory responses, and propose this signaling as a potential therapeutic target for IA treatment