A computational technique is introduced to reveal the complex intrinsic structure of homoclinic and heteroclinic bifurcations in a chaotic dynamical system. This technique is applied to several Lorenz-like systems with a saddle at the center, including the Lorenz system, the Shimizu-Morioka model, the homoclinic garden model, and the laser model. A multi-fractal, self-similar organization of heteroclinic and homoclinic bifurcations of saddle singularities is explored on a bi-parametric plane of those dynamical systems. Also a great detail is explored in the Shimizu-Morioka model as an example. The technique is also applied to a re exion symmetric dynamical system with a saddle-focus at the center (Chua's circuits). The layout of the homoclinic bifurcations near the primary one in such a system is studied theoretically, and a scalability ratio is proved. Another part of the dissertation explores the intrinsic mechanisms of escape in a reciprocally inhibitory FitzHugh-Nagumo type threecell network, using the phase-lag technique. The escape network can produce phase-locked states such as pace-makers, traveling-waves, and peristaltic patterns with recurrently phaselag varying.

Networks at various levels of the nervous system coordinate different motor patterns such as respiration, eye or hand movements and locomotion. Intrinsic rhythm-generating networks that are located in the spinal cord generate motor behaviors that underlie locomotion in vertebrates. These networks give a continuous and measurable coordinated rhythmic motor output and are referred to as locomotor central pattern generators (CPGs). Characterization of the mammalian locomotor CPG and its molecular control is depending on the identification of participating neurons and neuronal populations. In this thesis I present work where we have studied the significance of subpopulations of neurons in the formation and function of the left-right circuitry. In summary, we show that the axon guidance receptor DCC has a central role in the formation of spinal neuronal circuitry underlying left-right coordination, and that both Netrin-1 and DCC are required for normal function of the locomotor CPG. Commissural interneurons (CINs), which send their axons across the ventral midline in the spinal cord, play a critical role in left–right coordination during locomotion. A complete loss of commissural axons in the spinal cord, as seen in the Robo3 null mutant mouse, resulted in uncoordinated fictional locomotor activity. Removing CIN connections from either dorsal or ventral neuronal populations led to a shift from alternation to strict synchronous locomotor activity. Inhibitory dI6 CIN have been suggested as promising candidate neurons in coordinating bilateral alternation circuitry. We have identified that Dmrt3, expressed in inhibitory dI6 CINs, is a crucial component for the normal development of coordinated locomotor movements in both horses and mice. We have also concluded that the prominent hopping phenotype seen in hop/hop mice is a result of abnormal developmental processes including induction from the notochord and Shh signaling. Together, these findings increase our knowledge about the flexibility in neuronal circuit development and further confirm the role of dI6 neurons in locomotor circuits.

München, Techn. Univ., Diss., 2004.

Thesis (Ph.D.)--Medical University of Ohio, 2006. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Michael A. Pereira. Includes abstract. Document formatted into pages: v, 152 p. Title from title page of PDF document. Title at ETD Web site: Involvement of DNA methylation and CpG endonuclease activity in environmental carcinogenesis and cancer chemoprevention. Bibliography: pages 65-66, 90-92, 123-125, 137-150.

Techn. Universiẗat, Diss., 2003--Berlin.

Abstract As the defects in DNA repair and cell cycle control are known to promote tumorigenesis, a proportion of inherited breast cancers might be attributable to mutations in the genes involved in these functions. In the present study, three such genes, TP53, CHK2 and ATM, which are also associated with known cancer syndromes, were screened for germline mutations in Finnish breast cancer patients. In combination with our previous results, three TP53 germline mutations, Tyr220Cys, Asn235Ser and Arg248Gln, were detected in 2.6% (3/108) of the breast cancer families. The only observed CHK2 alteration with a putative effect on cancer susceptibility, Ile157Thr, segregated ambiguously with the disease, and was also present in cancer-free controls. The available functional data, however, suggests that the altered CHK2 in some way promote tumorigenesis. Furthermore, compared to the other studied populations, Ile157Thr seems to be markedly enriched in Finland. Thus, the clinical significance of Ile157Thr requires further investigation among Finnish cancer patients. ATM germline mutations appear to contribute to a small proportion of the hereditary breast cancer risk, as two distinct ATM mutations, Ala2524Pro and 6903insA, were found among three families (1.9%, 3/162) displaying breast cancer. They all originated from the same geographical region as the AT families with the corresponding mutations, possibly referring to a founder effect concerning the distribution of these mutations in the Finnish population. The genes important for tumorigenesis in sporadic disease might also contribute to familial breast cancer. Therefore, four putative LOH targets genes in chromosome 11q21-q24 were screened for intragenic mutations, and five were analyzed for epigenetic inactivation in sporadic breast tumors. The lack of somatic intragenic mutations in MRE11A, PPP2R1B, CHK1 and TSLC1 led us next to investigate promoter region hypermethylation as a mechanism capable of silencing these genes, as well as the ATM gene. Only TSLC1 demonstrated involvement of CpG island methylation, which was especially prominent in three tumors. This suggests that together with LOH, methylation could result in biallelic inactivation of the TSLC1 gene in breast cancer.

No description available.

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8620&pubmed-linkout=1 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19927号 / 医博第4147号 / 新制||医||1017(附属図書館) / 33013 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 泰広, 教授 妹尾 浩, 教授 武田 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第20309号 / 薬科博第78号 / 新制||薬科||8(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 髙倉 喜信, 教授 橋田 充, 教授 山下 富義 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Internet users generally feel their actions are anonymous, but this is often not the case. Users can be tracked and their actions logged for future analysis, which is not the desire of most users. Software and services exist which offer anonymity on the Internet when used correctly. Anonymity on the Internet is useful for many people including whistleblowers, dissidents, law enforcement, and the security conscious, but it can be abused. A user can act maliciously under the guise of anonymity without the fear of retribution. Thus, a level of administrative control over users is desirable, even in an anonymous system. Administrative control over users in an open, anonymous system is extremely difficult, but what about a closed, pseudonymous system? Closed Pseudonymous Groups is a pseudonymous framework for a closed group of users that balances the needs of the user with those of a service administrator. Using a resource that uniquely identifies a user, the user may create a pseudonym with which they can interact with the service over the Internet. Misbehaving pseudonyms can be blocked from using the service, and the offending user is unable to create a new authorized pseudonym.