Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 99-108).

Thesis--Uppsala. / In Periodical Room.

O benzeno é um solvente comprovadamente cancerígeno e, para substâncias com tal característica, não há limites de exposição considerados seguros. Em vista disso, as discussões internacionais e nacionais visam a diminuir, cada vez mais, os níveis de exposição ocupacional permitidos. O ácido trans, trans-mucônico (ttAM) , um produto de biotransformação do benzeno, tem sido preconizado como um bioindicador sensível da exposição ao solvente. Este trabalho foi desenvolvido com o propósito de validar método capaz de detectar o ttAM em urina de indivíduos expostos ao benzeno, bem com estabelecer o melhor período de coleta das amostras. A técnica escolhida foi a cromatografia líquida de alta eficiência (CLAE) com coluna de fase-reversa, Lichrosorb RP 18, e detector de ultra-violeta. O método mostrou-se linear entre 0,2 a 5,0 mg/L (r2 = 0,9943). Os limites de detecção e de quantificação obtidos foram, respectivamente, 0,1 e 0,2 mg/L. A porcentagem de recuperação absoluta média foi de 77,1% e de inexatidão de 27,9%. Os coeficientes de variação médios foram, para a precisão intra-ensaio 7,7 % e, para a interensaio 10,6%. O analito permaneceu estável na matriz por um período de 6 semanas para a concentração de 0,2 mg/L e de 15 semanas, para a 2,0 mg/L, se armazenada em freezer (-20°C) e por até dez dias sob refrigeração (4°C) para os adicionados de 0,2, 2,0 e 5,0 mg/L. Com estes resultados, a validação foi considerada satisfatória. O valor médio obtido nas amostras de trabalhadores ocupacionalmente expostos no final da jornada de trabalho foi de 0,81 mg/g creatinina (mediana=0,62 mg/g creatinina). Estes resultados foram superiores e estatisticamente diferentes (p=0,025) daqueles encontrados em amostras do início da jornada e do dia seguinte, mostrando ser o final da jornada o período que melhor reflete a exposição do dia de trabalho. / Benzene is a carcinogenic chemical used in many plants. The national and international discussions aim to low more and more the permitted occupational exposure limit to benzene, although in fact, there is no safe limit to carcinogens. The trans, trans-muconic acid (ttMA), a benzene metabolite, has been recommended as a sensitive bioindicator in the biological monitoring of workers exposed to this solvent. This work was developed in order to validate a method for ttMA analysis in samples of benzene-exposed workers as well as to establish the best sample collecting time. The chosen technique was the high pressure liquid chromatography with reverse-phase column, Lichrosorb RP 18, and UV detection. A linear relationship (r2 =0.9943) was observed in the range from 0.2 to 5.0 mg/L. The detection and quantification limits were respectively 0.1 and 0.2 mg/L. The average recovery was 77.1 % and the inaccuracy (bias) was 27.9 %. Precision, evaluated by variation coefficient, were 7.7 % (intraassay) and 10.6 % (inter-assay). The ttMA remained stable in the matrix during a period of six weeks for the 0.2 mg/L samples and fifteen weeks for the 2.0 mg/L samples, in both cases when stored at - 20°C. In 0.2, 2.0 and 5.0 spiked samples no significant differences were found when conserved at 4°C for ten days. In the occupationally exposed workers, ttMA values were significantly higher in post-shift samples (p = 0.025) than in pre-shift or in those collected in the following day. These results reveal that the end of the shift is the best period to take urine samples for benzene biomonitoring.

[No abstract submitted] / Science, Faculty of / Physics and Astronomy, Department of / Graduate

No description available.

No description available.

In the thesis, the development of asymmetric organocatalytic [3+3] sequences for the assembly of aminocyclitols is described. A water-based Wittig reaction was developed in order to produce the key enal-based starting materials, which were otherwise difficult to obtain commercially and synthetically. The enals derived from the Witig reaction were employed in the synthesis of both natural products and synthetic analogs of compounds in the amaryllidaceae family. The [3+3] Michael-aldol sequence described herein provided regio-, diastereoand enantioselective access to the core of the various targeted molecules, containing 3 to 4 defined stereocenters. The sequence was optimized via manipulation of the structures of both the organocatalyst and base used leading to increased selectivity and yield. Complete total synthesis of the natural product (+)-trans-dihydrolycoricidine was achieved using the optimized organocatalytic Michael-aldol sequence. The most effective catalyst/base combination for this synthesis was found to be a comercial diphenylsilylprolinol ether and quinidine, which led to a dramatic reduction in the number of synthetic steps taken to the final product, and highest yield, when compared to other reported approaches: in 9 chemical steps, 12% overall yield and 98% e.e. were achieved. Two non-natural analogues were also synthesized using this methodology in order to probe the minimum pharmacophore of the amaryllidaceae derivatives, as they are known to express anti-viral and anti-cancer activity for certain cell lines. (+)-3- Deoxydihydrolycoricidine containing 4 chiral centers, was synthesized via the same [3+3] Michael-aldol sequence as the natural product in 6 steps with 15% yield and >99% e.e. Similarly, (+)-trans-3-epidihydrolycoricidine was obtained in 6 steps, 27% yield and >99% e.e. The biological activity of these derivatives is yet to be examined. This highly effective method for the preparation of chiral aminocycllitols can be generalized toward the synthesis of numerous targets, which will be the focus of future research. / Thesis / Doctor of Philosophy (PhD)

No description available.

Das Ziel dieser Arbeit bestand darin, herauszuarbeiten, welche Kompetenzen Fach- kräfte benötigen, um trans* Jugendliche in der stationären Jugendhilfe angemessen und kinderschutzsensibel zu begleiten. Zu Beginn wurde das Handlungsfeld der Kinder- und Jugendhilfe beleuchtet, um den Auftrag der Fachkräfte klarer zu defi- nieren: Es geht darum, Kinder und Jugendliche in ihrer Entwicklung zu unterstützen und sie auf ein selbstständiges Leben vorzubereiten. Im Kontext des §34 SGB VIII wird der Schutzauftrag, den Fachkräfte gegenüber diesen Jugendlichen haben, zu einer grundlegenden Verpflichtung, da der Schutz des Kindeswohl von größter Be- deutung ist. Der Begriff des Kindeswohl wurde dementsprechend analysiert und de- finiert. Hervorzuheben ist die Reformierung des §9 SGB VIII im Jahr 2021, weil trans* Jugendliche explizit erwähnt werden und damit der Handlungsbedarf für Fachkräfte im Umgang mit dem Thema Trans*identität verstärkt wird.:1. Einleitung 1 2. Handlungsfeld Kinder- und Jugendhilfe 6 2.1. Hilfen zur Erziehung: §34 Heimerziehung, sonstige betreute Wohnform 7 2.2. Rechtliche Grundlage: SGB VIII und Kindeswohl 8 3. Theoretischer Rahmen 12 3.1. Geschlecht und Geschlechtsidentität 12 3.2. Trans*identität 14 3.2.1. Begrifflichkeiten 14 3.2.2. Binäres Geschlechtersystem und Heteronormativität 16 3.2.3. Transsexuellengesetz, Selbstbestimmungsgesetz 18 3.3. Kindes- und Jugendalter 20 3.3.1. Adoleszenz, Pubertät, Identitätsentwicklung 20 3.3.2. Trans*identität im Jugendalter 23 3.4.1. Intersektionalität 27 3.4.2. Diskriminierung 29 3.4.3. Besondere Herausforderungen für trans* Jugendliche 30 4. Herausforderungen in der stationären Jugendhilfe 35 4.1. Herausforderungen für trans* Jugendliche in der stationären Jugendhilfe 35 4.2. Grenzen der stationären Jugendhilfe 38 4.3. Handlungsempfehlungen für stationäre Einrichtungen 41 5. Fazit 48 Literaturverzeichnis 51

Computational techniques, mostly density functional theory (DFT), were applied to study metal-based catalytic processes for energy conversion reactions. In the first and second projects, the main focus was on activation of the light alkanes such as methane, which have thermodynamically strong and kinetically inert C–H bonds plus very low acidity/basicity. Two Mo-oxo complexes with the different redox non-innocent supporting ligands, diamide-diimine and ethylene-dithiolate, were modeled. These Mo-oxo complexes are modeled inspired by active species of a metalloenzyme, ethylbenzene dehydrogenase (EBDH). The results for the activation of the benzylic C–H bond of a series of substituted toluenes by modeled Mo-oxo complexes show there is a substantial protic character in the transition state which was further supported by the preference for [2+2] addition over HAA for most complexes. Hence, it was hypothesized that C–H activation by these EBDH mimics is controlled more by the pKa than by the bond dissociation free energy of the C–H bond being activated. The results suggest, therefore, promising pathways for designing more efficient and selective catalysts for hydrocarbon oxidation based on EBDH active site mimics. Also, it is found that the impact of supporting ligand and Brønsted/Lowry acid/base conjugate is significant on the free energy barrier of C–H bond activation. In the third project the focus was on assessing the nature of hydrogen in the transition state related to the transfer of hydrogen between a carbon and nitrogen in an experimentally studied hydroaminoalkylation process by a five-coordinate Ta complex. It was revealed that, for the studied substituents, pKa is a larger driving force in the rate-determining hydrogen transfer reaction than the BDFE, which suggest a reasonable amount of protic character in the transition state, and possible routes to the design of more active catalysts with greater substrate scope. Finally, for the last project, the focus was on hydrotris(1,2,4-triazol-1-yl)borate complex as an electrocatalyst and study the impact of metal identity down a group or across a period of the d-block on proton-coupled electron transfer (PCET), which is a key process in many electrocatalytic cycles. The studied thermodynamics and kinetics trends for a series of mid to late 3d- and 4d-transition metals show the metal and its electronic structure greatly impact the nature of the PCET processes.