ユーザ嗜好に基づく情報検索・フィルタリングに関する研究

制度:新 ; 文部省報告番号:乙2057号 ; 学位の種類:博士(工学) ; 授与年月 日:2006/12/21 ; 早大学位記番号:新435

Functional Amyloid Formation within Mammalian Tissue

Amyloid is a generally insoluble, fibrous cross-β sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin—a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology

A Comparative Look at Immigration and Human Capital Assessment

This article examines the formation of an immigration policy designed to build up the skill and human capital of a country. We discuss how the process of selecting economic-stream migrants could be designed to yield economic benefits to the host country. Part I examines the theoretical considerations involved in framing a policy that governs economic-stream immigration. In this section, we outline the goals that a host country seeks to achieve in selecting these migrants and propose important elements of a selection scheme. Part II takes a comparative look at existing points-based schemes for selecting economic migrants, focusing on Canada and Australia. Part III briefly discusses practical barriers to implementing such a system in the United States. The article concludes that the United States should enact a points-based system for selecting economic-stream migrants. It is impossible to cover this subject exhaustively in one article. For that reason, this article only discusses the immigration of high-skilled workers, not low-skilled or agricultural workers. We also only discuss permanent immigration, not temporary workers. Finally, as others studying this area know, we are all handicapped by a lack of good statistical or economic data. We discuss several studies that have sought to evaluate the economic success of economic-stream migrants over time, but these studies are limited in scope, the time period covered, and their ability to establish a clear link between selection criteria and the economic results that were measured. Thus, our recommendations should be considered skeptically. As discussed below, we are not sure what has worked best in other countries, let alone how policy changes would work in the U.S. context

Development of methods for the determination of bismuth and thallium in geological materials and their significance for the Cretaceous-Tertiary boundary event : a thesis presented in partial fulfilment for the degree of Master of Science, Department of Chemistry and Biochemistry, Massey University, New Zealand

Solvent extraction methods have been developed for the determination of thallium and bismuth in rocks. The method for thallium is based on the extraction of the chlorocomplex into methylisobutyl ketone followed by removal of the interfering chloride ion as insoluble silver chloride. The method for bismuth is based on the extraction of a stable metal complex with ammonium pyrrolidine dithiocarbamate into methylisobutyl ketone. Both elements are analysed on a electrothermal graphite furnace atomic absorption spectrometer. Tests on the efficiencies of the methods showed a good precision and accuracy with limits of detection of 9.5 ng/ml (ppb) for thallium and 20 ng/ml (ppb) for bismuth. Recovery studies on synthetic samples showed recoveries of >99.9% for both elements. A geochemical study was performed on a Cretaceous-Tertiary boundary site located near Flaxbourne River, Ward, New Zealand. Investigations were carried out to determine the enrichment of thallium and bismuth in the stratigraphic column. The results show a good correlation between the iridium and thallium content throughout the rock sequence, but the samples have very low bismuth contents. This is indicative of the different geochemical behavior of bismuth to other chalcophiles. These findings do not contradict the impact theory initially hypothesized by Alvarez et al. (1980), and instead suggest that bismuth's mobility and solubility are far greater than those of thallium and the other chalcophile elements enriched in the Flaxbourne River sequence. This results in the leaching of bismuth from the stratigraphic column by sea water after deposition

In vitro induction of melanin synthesis and extrusion by tamoxifen

Physical appearance has significant importance psychologically and socially, with skin and hair being of prime relevance. Effective ingredients that modulate melanin synthesis are of growing interest. Tamoxifen, a widely used selective oestrogen receptor modulator, SERM, was described occasionally in medical case reports as causing grey hair repigmentation. This work aimed to study, in vitro, the effect of tamoxifen and 4-hydroxy-tamoxifen, one of its most bioactive derivatives, on melanin production in human melanocytes.Teresa Matam a holds a grant from FCT–Fundação para a Ciência e a Tecnologia (SFRH/BPD/47555/2008). This work was supported by FEDER through POFC–COMPETE and by national funds from FCT through the project PEst-C/BIA/UI4050/2011

Breath acetone concentration decreases with blood glucose concentration in type I diabetes mellitus patients during hypoglycaemic clamps

Conventional wisdom is that breath acetone may be markedly elevated in type 1 diabetes, but that this only occurs during poor blood glucose control and/or intercurrent illness. In contrast, little is known about breath acetone at more representative everyday blood glucose levels in diabetes. We used selected ion flow tube mass spectrometry (SIFT-MS) to monitor the breath of 8 patients with type 1 diabetes mellitus during “insulin clamp” studies in which insulin and glucose were infused into patients to lower blood glucose levels in steps from normal values into the low glucose (hypoglycaemic) range. The concentration of acetone in breath and the blood sugar concentration of the patients were monitored at each blood glucose concentration. The blood glucose level at the start of the study was typically about 6mM/L, whereas the breath acetone concentration at this blood glucose level was unexpectedly variable, ranging from one part-per-million (ppm) to 21 ppm, in contrast to what was previously believed, i.e. that type 1 diabetes mellitus (T1DM) is characterised by high acetone levels. In all 8 patients, the breath acetone declined linearly with blood glucose concentration