Lutein is a principal constituent of the human macular pigment. This study is composed of two projects. The first studies the conformational geometries of lutein and its potential adaptability in biological systems. The second is a study of the response of human subjects to lutein supplements. Using semi-empirical parametric method 3 (PM3) and density functional theory with the B3LYP/6-31G* basis set, the relative energies of s-cis conformers of lutein were determined. All 512 s-cis conformers were calculated with PM3. A smaller, representative group was also studied using density functional theory. PM3 results were correlated systematically to B3LYP values and this enables the results to be calibrated. The relative energies of the conformers range from 1-30 kcal/mole, and many are dynamically accessible at normal temperatures. Four commercial formulations containing lutein were studied. The serum and macular pigment (MP) responses of human subjects to these lutein supplements with doses of 9 or 20 mg/day were measured, relative to a placebo, over a six month period. In each instance, lutein levels in serum increased and correlated with MP increases. The results demonstrate that responses are significantly dependent upon formulation and that components other than lutein have an important influence serum response.

The work in this thesis mainly focuses on the assessment of density functional methods for computing structures and energies of organic and bioorganic molecules. Previous studies found dramatic conformational and stability changes from B3LYP to MP2 geometry optimization for some Tyr-Gly conformers. Possible reasons could be large intramolecular basis set superposition errors (BSSEs) in the MP2 calculations and the lack of dispersion in the B3LYP calculations. The fragmentation method and three kinds of rotation methods were used to investigate intramolecular BSSE. It is concluded that the rotation method cannot be used to correct intramolecular BSSE along a rotation profile. Another methodology is to employ modern density functionals. We focused on M06-L with the Tyr-Gly conformer ‘book6’. Potential energy profiles were determined by computing the energy for geometries optimized at various fixed values of a distance that controls the degree of foldedness of the structure. M06-L manifested itself as a very promising method to investigate the potential energy surface of small peptides containing aromatic residues. To predict Tyr-Gly structures, 108 potential conformers were created with a Fortran program. The geometry optimizations were done using M06-L/6-31G(d) and M05-2X/6-31+G(d). Two schemes were employed and the most stable conformers were compared to the 20 stable conformers found by B3LYP. Both schemes found 10 conformers similar to one of the B3LYP stable conformers, as well as several newly found conformers. The study of a missing B3LYP stable conformer showed that the possible reason of missing conformers may be the lack in dispersion in B3LYP theory. To study the hydration effect, we studied the conformations of neutral and zwitterionic 3-fluoro-γ-aminobutyric acid (3F-GABA) in solution using different solvation models, mainly the explicit water molecule models. Zwitterionic forms of 3F-GABA are preferred in solution. M06-2X performs better in calculating transition energy profiles than MP2.

What various roles exist in corporate toxicity? In what environment does toxicity thrive? Do toxic leaders exhibit certain characteristics? Questions such as these can be discovered using this classroom tool! / This case study provides a real-world example of corporate toxicity to illustrate the toxic triangle model and show how situations like this one come to pass (Padilla, 2013). The primary focus will be on WorldCom/MCI and the events leading to the world famous accounting scandal that came to light in 2003. This case briefly examines the three major triangle elements, (1) the role of the leader, (2) the enabling efforts of colluding and conforming followers, and (3) the conducive nature of the specific organizational context, all in correlation with the eventual destruction of the organization. Identifying these elements provides an opportunity for students to analyze an actual account of corporate toxicity through critical thinking and discussion. The questions provided are intended to stimulate a discussion focused on the: (1) events leading to the demise of the organization, (2) characteristics of the primary leader and followers, (3) role the environment played in escalating the situation, and (4) the influences of social pressures.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第22505号 / 農博第2409号 / 新制||農||1077(附属図書館) / 学位論文||R2||N5285(農学部図書室) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 保川 清, 教授 宮川 恒, 教授 入江 一浩 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

No description available.

Memory of chirality (MOC) is an emerging strategy in asymmetric synthesis. It has been applied to enolate chemistry, reactions involving carbocation intermediates, and to radical systems. In this strategy the chirality of an enantiopure reactant is transferred to the dynamic chirality of a reactive intermediate to produce stereospecific product. 1,4-Benzodiazepin-2-ones have been described as a "privileged" structure in medicinal chemistry. In addition to their uses as anxiolytics (Valium ®) and anti-epileptic agents (Clonopin ®), they have shown activity as HIV Tat antagonist, ras farnesyltransferase inhibitors in cancer cells, and antiarrhythmic agents. Because of the utility of this scaffold in the area of medicinal chemistry, it has served as a template in libraries for tens of thousands of compounds. Despite the vast diversity of 1,4-benzodiazepin-2-ones, there are few routes to enantiomerically enriched 3,3-disubstituted benzodiazepines containing a "quaternary" stereogenic center. This research will discuss the stereochemical properties of 1,4-benzodiazepin-2-ones, and provide a novel approach to synthesize enantiomerically enriched "quaternary" benzodiazepines with stereogenic centers through MOC, without the use of external chiral sources. / Ph. D.

Speech recognition is the task where a machine processes human speech into a written format. Groundbreaking scientific progress within speech recognition has been fueled by recent advancements in deep learning research, improving both key metrics of the task; accuracy and speed. Traditional speech recognition systems listen to, and analyse, the full speech utterance before making an output prediction. Streaming speech recognition on the other hand makes predictions in real- time, word by word, as speech is received. However, the improved speed of streaming speech recognition comes at a cost of reduced accuracy given the constraint of not having access to the full speech utterance at all time. In this thesis, we investigate the accuracy of streaming speech recognition systems by implementing models with state-of-the-art Transformer-based architectures. Our results show that for two similar models, one streaming, the other non-streaming, trained on a 100hr subset of Libirspeech, achieve a word error rate of 9.99%/10.76% on test- clean without using a language model. This puts the cost of streaming at a 7.2% accuracy degradation. Furthermore, the streaming models can be used “on-device” which has many benefits, including lower inference time, privacy preservation, and the ability to operate without an internet connection. / Taligenkänning är uppgiften där en dator bearbetar mänskligt tal till ett skrivet format. Forskning inom taligenkänning har drivits av de senaste framstegen inom forskning i djupinlärning, vilket har lett till att de två viktigaste mätvärdena, träffsäkerhet och hastighet, har förbättrats. Traditionella taligenkänningssystem lyssnar till och analyserar hela talsekvensen innan en prediktion görs. Strömmande taligenkänning å andra sidan gör realtids prediktioner, ord för ord, när tal tas emot. Den ökade hastigheten som strömmande taligenkänning medför kommer på bekostnad av träffsäkerhet då tillgången till hela talsekvensen inte alltid är tillgänglig. I den här avhandlingen undersöker vi träffsäkerhet av strömmande taligenkänningssystem genom att implementera ”Transformer”- baserade arkitekturer. Våra resultat visar att för två liknande modeller, en strömmande, och en icke- strömmande, tränade på 100 timmar av datasetet Librispeech, når en ordfelfrekvens på 9.99%/10.76% på ”test-clean”. Det gör att strömmande taligenkänning kommer på en bekostnad av 7.2% träffsäkerhet jämfört med icke- strömmande. De strömmande taligenkänningsmodellerna kan användas ”on-device” vilket främjar lägre slutledningstider, sekretessbevarande och förmågan att fungera utan internetanslutning.

Le cannabidiol (CBD), constituant majeur non-psychotrope du Cannabis sativa, possède un grand nombre de propriétés pharmacologiques. Des dérivés du CBD présentant une rotation restreinte autour de la liaison simple aryl-C(sp3) ont été synthétisés avec deux modifications majeures apportés sur l’un ou/et l’autre cycle dans le but d’atteindre et de contrôler l’atropisomérie.Des phénylcyclohexanes diversement substitués ont été préparés par hydrogénation catalytique des phénylcyclohexènes correspondants. Des études de RMN dynamique et de modélisation moléculaire ont permis l’identification des épimères (1R/1S) et de leurs conformères (M/P). Selon la nature des substituants, de bons résultats de diastéréosélectivité et d’atroposélectivité ont été obtenus. Les conformères de l’épimère (1S) ont des barrières de rotation élevées jusqu’à 92 kJ.mol-1, contrairement à ceux de (1R) avec des barrières de seulement ~72 kJ.mol-1. L’atropisomérie dépend non seulement des substituants autour l’axe de chiralité mais aussi de la position d’un groupe méthyle sur le cycle monoterpénique (en C1).Des dérivés ortho-soufrés ont été préparés à partir de leurs analogues oxygénés via le réarrangement de Newman-Kwart. La substitution de l’atome d’oxygène par le soufre ralentit significativement l’échange conformationnel, les barrières énergétiques augmentent d’environ 10 kJ.mol-1. / Cannabidiol (CBD) is the major non-psychoactive constituent of Cannabis sativa with a large number of pharmaceutical interests. CBD derivatives with restricted rotation about the aryl-C(sp3) single bond have been synthesized with two major changes on one and/or both cycles in order to reach and control atropisomerism.Diversely substituted phenylcyclohexanes were prepared by catalytic hydrogenation from their corresponding phenylcyclohexenes. Dynamic NMR experiments and DFT calculations allowed us to identify the epimers (1R/1S) and their conformers (M/P). According to the nature of the substituents, high diastereoselectiviy and atrop-selectivity were obtained in these natural product derivatives. The conformers of epimers (1S) show high rotational barriers of up to 92 kJ.mol-1, unlike those of (1R) and with much lower barriers of ~72 kJ.mol-1. Atropisomerism not only depends on the substituents at the axis of chirality but also is influenced by the position of a methyl group on the monterpene ring (at C1).Ortho-thio derivatives were prepared from their oxygenated analogs via the Newman-Kwart rearrangement. The substitution of the oxygen atom by the sulfur slows the conformational exchange significantly increasing the rotational barriers of around 10 kJ.mol-1.