Each year, between 300 and 500 million people develop malaria. Close to 3 million people die as a result. Due to resistance there are now few drugs left which are effective against malaria; one is a Chinese herbal remedy called qinghaosu (artemisinin). A section of this thesis represents an attempt to understand further the mode of action of this antimalarial agent. Several mechanisms involving iron have been proposed and the main categories reviewed (chapter 3). Techniques including ESR spectrometry, fluorescence and absorbance measurements were used to further probe the mode of action of qinghaosu. The findings of these studies provide support for a mechanism proposed by Wu et al., involving cleavage of the peroxy bridge in qinghaosu with the ferrous ion as opposed to antimalarial activity being due to the generation of high valent iron-oxo species. The ether derivative of qinghaosu, arteether has been studied using 2D NMR in order to provide further insight into the unusual structure of this compound (chapter 4). A comparison of the sp2 lactone functionality in qinghaosu with the sp3 ether group in arteether was performed. Evidence is presented for different conformations and chemical shift values. The immune system protects the human body from invasion by foreign substances or cells. A key part of this immune response comes from cellular components known as macrophages. The killing process of macrophages appears to involve nitric oxide. However, this natural defence mechanism is not very efficient as the body is susceptible to invasion by microbes. The term microbe includes both parasites and bacteria. The toxicity of nitric oxide (NO) and NO donor compounds has been investigated using the bacterium E. coli (chapter 5). In addition, studies have been performed using parasites. Malarial parasites (Plasmodia) are difficult to culture, therefore Leishmania parasites which cause the tropical disease leishmaniasis were used as a model (chapter 6). Evidence is presented for the toxic nature of NO donor compounds towards both parasites and bacteria. However, qinghaosu and its derivatives did not prove effective against Leishmania mexicana parasites in contrast with their reported antimalarial activity. The conclusions of this study suggest that qinghaosu possesses a toxicity mechanism selective for malarial parasites.

Observations of the ß Cephei star 12 Lacertae have been made at both high time and spectral resolution with an Image Isocon television camera. The observations cover complete cycles of the pulsation on two consecutive nights in October 1972. The spectral region covered includes the two Si III inclines at λ 4553 and λ 4568. The line profile variations have been studied in detail; in particular the line doubling at certain phases of the pulsation. Wavelength shifts of the separate components were measured and a discontinuous radial velocity curve was obtained. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

The Georgia Institute of Technology (Georgia Tech), one of the nations leading engineering schools, has limited institutional history of collaboration with surrounding K-12 schools. K-12 outreach is not a part of Georgia Techs mission, though recent years have seen greater outreach activities. Campus organizations have sponsored tutoring, academic schools have sponsored recruitment fairs and the College of Engineering has established a partnership with a high school. Two offices within Georgia Tech, the Center for the Enhancement of Teaching and Learning (CETL) and the Center for Education Integrating Science, Math and Computers (CEISMC), have been working to expand and deepen Georgia Techs K-12 outreach through a National Science Foundation grant program combining graduate student development and K-12 outreach. Through this program, the Student and Teacher Enhancement Partnership (STEP), CETL and CEISMC seek to build meaningful and lasting relationships between Georgia Tech and local high schools. Given the novelty of mutually rewarding relationships between Georgia Tech and local high schools, this study attempts to account for differences in outcomes of the (STEP) program over its first three years. STEPs Project Officers at Georgia Tech developed dyadic relationships with high school personnel with the same programmatic goals in mind. However, at the end of three years, some of these pairings were more mutually rewarding. A narrative analysis of these relationships is presented through case studies and tested against a literature-based logic model depicting factors likely to lead to successful, inter-organizational partnerships.

Um die Rolle von Interleukin-12p75 (IL-12p75) und Interleukin-12p40 (IL-12p40) in der Abwehr einer Kryptokokken-Infektion im Mausmodell zu untersuchen, wurden Mäuse auf 129Sv/Ev Stammhintergrund intraperitoneal und intranasal mit Cryptococcus neoformans (C. neoformans) infiziert. Dabei wurden die Unterschiede im Infektionsverlauf und in der Immunreaktion von Wildtyp-, IL-12p35-/- und IL-12p35/p40-/--Mäusen analysiert. Unterschiede zwischen den Wildtyp- und den IL-12p35-/--Mäusen lassen auf die Bedeutung von IL-12p75 schließen, wogegen Unterschiede zwischen IL-12p35-/-- und IL-12p35/p40-/--Mäusen auf die Rolle von IL-12p40 schließen lassen. Untersucht wurden sowohl die Erregerkonzentration in den Organen, Antigenspiegel im Blut, histologische Veränderungen und Serumantikörperkonzentrationen. Nach intraperitonealer Infektion war die Keimbelastung der Organe bei den Wildtyp-Mäusen geringer als bei beiden IL-12-/--Mausstämmen. Bei Wildtyp-Mäusen waren nicht nur weniger lebende Kryptokokken in den Organen zu finden, sondern auch weniger Kryptokokken Antigen im Serum als bei beiden IL-12-/--Mäusen nachweisbar. Das zeigt, dass IL-12p75 für die Kontrolle der intraperitonealen Infektion mit C. neoformans notwendig ist. IL-12p40 hatte ähnlich wie IL-12p75, wenn auch in etwas geringerem Masse, eine protektive Rolle bei der Erregerabwehr. Ohne IL-12p40 war eine Kontrolle der Infektion auf einem geringen Niveau der Keimbelastung nicht möglich. Besonders deutlich wurde dieses Phänomen beim Antigentiter bei den IL-12p35/p40-/--Mäusen. Durch das Fehlen von IL 12p40 wurde bei den IL-12p35/p40-/--Mäusen viel mehr Antigen über das Blut im Serum verteilt als bei den IL-12p35-/-- oder den Wildtyp-Mäusen. Die Wirtsreaktion bei einer Infektion mit C. neoformans geht mit der Bildung von Granulomen einher. Ohne IL-12p75 kam es zwar noch zur Bildung von Granulomen, diese zeigten aber eine veränderte zelluläre Zusammensetzung. Die IL-12p35/p40-/--Mäuse waren nicht zur Ausbildung von typischen Granulomen fähig. Bei ihnen kam es zu einer vermehrten Ansammlung von Kryptokokken fast ohne Entzündungszellen. IL-12p40 ist also für die Ausbildung einer zellulären Entzündungsreaktion notwendig. IL-12p40 ist auch für die Antikörperbildung gegen C. neoformans erforderlich. Die IL 12p35/p40-/--Mäuse waren kaum in der Lage, spezifische Antikörper gegen C. neoformans zu bilden. IL-12p75 ist für die Ausbildung einer Th1-Antwort notwendig. Infizierte Wildtyp-Mäuse produzierten doppelt soviel IgG2a, welches für ein Th1-Antwort typisch ist, wie die IL 12p35-/--Mäuse. Der intranasale Infektionsweg kommt der natürlichen aerogenen Infektion recht nahe. Deshalb wurde – zusätzlich zur intraperitonealen Infektion - dieser Infektionsweg zur Untersuchung der Immunantwort gegen C. neoformans berücksichtigt. Auch bei intranasaler Infektion ist IL-12p75 für die Kontrolle der Keimbelastung der Organe notwendig. Interessanterweise war die Keimbelastung der Lunge bei den IL-12p35-/--Mäusen etwas höher als bei den IL-12p35/p40-/--Mäusen. Bei den Wildtypmäusen war die Dissemination der Kryptokokken aus der Lunge in die Milz und ins Gehirn gering. Ein Fehlen von IL-12p75 bewirkte allerdings eine Besiedlung besonders des Gehirns. Nach intranasaler Infektion kam es in der Lunge von Wildtyp-Mäusen zu atypischen Granulomen mit zentraler Einschmelzung von Gewebe und Kryptokokken. Diese Reaktion war bei den IL-12p35-/--Mäusen noch stärker ausgeprägt als bei den Wildtyp-Mäusen. Bei den IL-12p35/p40-/--Mäusen blieb eine Gewebsreaktion größerer Areale aus. Es waren nur eine Aktivierung des BALT zu sehen. IL-12p40 ist demnach auch nach intranasaler Infektion für eine zelluläre Entzündungsreaktion notwendig. Möglicherweise kann sich diese Eigenschaft von IL-12p40 bei intranasaler Infektion in einer immunpathologischen Reaktion äußern, die bei IL-12p35-/--Mäusen für eine massive Infiltration der Lunge mit Entzündungszellen verantwortlich ist. Der Gehalt an Kryptokokken-spezifischen Antikörpern war nach intranasaler Infektion fünf- bis zehnmal höher als nach intraperitonealer Infektion. Der intranasale Infektionsweg zeigte also eine wesentlich ausgeprägtere humorale Antwort. Der Typ der Immunantwort schien sich im Gegensatz zur intraperitonealen Infektion in Richtung Th2 (d. h. verstärkte Antikörperbildung) verschoben zu haben. Sowohl nach intraperitonealer wie auch nach intranasaler Infektion mit C. neoformans lassen sich die immunstimulatorischen Aktivitäten von IL-12p75 und von IL-12p40 nachweisen, auch wenn diese sich in Abhängigkeit vom Infektionsweg etwas unterschiedlich manifestieren. / To analyse the role of interleukin-12p75 (IL-12p75) and interleukin-12p40 (IL-12p40) in the defence against Cryptococcus neoformans (C. neoformans) a murine infection model was established and studied. Mice of wild-tpye 129Sv/Ev background as well as IL-12p35-/- and IL-12p35/p40-/- 129Sv/Ev mice were infected intraperitoneally or intranasally with C. neoformans. The differences between the immune response of these genotypes were analysed. Comparing wild-type and IL-12p35-/--mice allows for conclusions related to the importance of IL-12p75, comparing IL-12p40-producing IL-12p35-/- mice with IL-12p35/p40-/- mice shows the importance of IL-12p40. Fungal organ burden, serum antigen levels, inflammatory cell responses, and antibody production were examined. The fungal organ load in wild-type mice was smaller than in both mutant IL-12-/--mice. In wild-type mice fewer cryptococci were found in organs and less cryptococcal antigen in serum than in IL-12p35-/- and IL-12p35/p40-/- mice. This underlines the importance of IL 12p75 for the control of the infection with C. neoformans. In addition, IL-12p40 was found to have a similar but weaker role as IL-12p75 in protection against C. neoformans. In the absence of IL-12p40 IL-12p35/p40-/- mice developed higher antigen titers than IL-12p35-/- and wild-type mice. The host response against infection with C. neoformans is associated with granuloma formation. Recruitment of inflammatory cells to granulomas was altered in the absence of IL 12p75. In addition, IL-12p40 contributed significantly to granuloma formation since IL 12p35/p40-/- mice developed no or only very poor granulomatous responses. Therefore, IL 12p40 is required for inflammatory cell responses. IL-12p40 was also found to be required for antibody production against C. neoformans. Infected IL-12p35/p40-/--mice had only very low levels of specific antibodies against C. neoformans. IL-12p75 is known to be essential for protective Th1 response against intracellular microorganisms. Th1 responses are commonly associated with the production of IgG2a. Infected wild-type mice produced 2-fold higher IgG2a levels than IL-12p35-/--mice. To adapt the infection model more to the natural infection mode the intraperitoneal infection route was changed to an intranasal route. Following intranasal infection IL-12p75 also proved to be necessary for control of the fungal organ load. Interestingly the organ load was higher in IL-12p35-/--mice than in IL-12p35/p40-/-mice which suggest a role of IL-12p40 in cell recruitment. Following intranasal application of cryptococci fungal dissemination to spleen and brain was reduced as compared to the intraperitoneal infection route. Without IL-12p75 dissemination of C. neoformans to the brain occured. This shows that IL-12p75 is involved in control of dissemination from lung to brain. The inflammatory response of IL-12p35-/--mice was stronger than the tissue response of wild-type mice. The massive tissue reactions of IL-12p35-/--mice caused big areas of diffuse cellular infiltration in their lungs. In IL-12p35/p40-/--mice inflammatory responses could be observed only in the peribronchial tissue. This shows that IL-12p40 is not only needed for a cellular inflammatory response following intraperitoneal but also following intranasal infection. Following intranasal infection IL-12p40 can induce immunopathological effects. Intranasal infection of mice with C. neoformans resulted in five to ten times higher antibody responses than intraperitoneal infection. This suggests that intranasal infection of mice results in a more Th2-biased humoral response. In summary, these experiments show that besides IL-12p75 also IL-12p40 contributes to cellular immunity against C. neoformans. The immunostimulatory properties of both, IL 12p75 and IL-12p40, can be observed after intraperitoneal and intranasal infection routes with similar but also distinct manifestations.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 91-100).

Föreliggande studie hade som syfte att genom en deduktiv tematisk analys av intervjumaterialet försöka utröna huruvida respondenternas upplevelse av den egna identiteten med fokus på självbild, självförtroende, självförmåga samt självkänsla har förändrats i och med att de genomgått 12-stegsprogrammet vid en svensk kriminalvårdsanstalt. Detta innebär att alla respondenterna har ett aktivt beroende bakom sig samt att de är intagna inom svensk Kriminalvård. De fördefinierade temana för frågorna gällande identitet var identitetsåtergång, identitetsutvidgning samt identitetsuppkomst. Utöver frågor gällande identitet så ställdes även frågor om respondenternas upplevelse av att genomgå 12-stegsbehandling inom anstalt. Orsaken till detta är att den speciella miljö där de genomgått 12-stegsbehandlingen kan ha påverkat utfallet av behandlingen. Denna analys var av en induktiv tematisk art och de teman som framkom är att respondenterna upplevde 12-stegsprogrammet som utvecklande men att det är besvärande med omotiverade deltagare samt att de i grupp känt sig hämmade med tanke på anstaltsmiljön.

The aim of this study is to understand and to assess the effects of river freshwater inflow on the circulation and dynamics of our region of interest, the Central Mediterranean Sea, both on shelf and basin scales, over short-term as well as long-term range. As far as we know this study provides the first investigation on river role on the Central Mediterranean overturning circulation. On the same time we point to improve the hindcast/forecast capability of our regional hydrodynamics model both on shelf and basin scales through a consistent representation of river inflow into the Central Mediterranean Sea taking not account all the physical processes involved in the local water cycle of specific catchments. An integrated modelling system including the atmosphere, the hydrology and the estuary dynamics has been set up upstream the regional ocean model at the Ofanto river outlet. The Estuary Box Model developed by the University of Connecticut (UCONN) jointly with the National Centre for the Atmospheric Research (NCAR) Climate Global Division and the University of Washington (UW) has been implemented for the selected case study, the Ofanto river, downstream of the meteo-hydrological chain and upstream of the regional ocean model. The model performance has been evaluated by comparison with a highly simplified approach based on Knudsen’s relation (Knudsen, 1900). Finally we built up an intermediate modelling approach.

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

The Terrestrial Ecosystem Model (TEM, version 4.0) was used to estimate net primary production (NPP) in China for contemporary climate and NPP responses to elevated CO₂ and climate changes projected by three atmospheric general circulation models (GCMs): Goddard Institute for Space Studies (GISS), Geophysical Fluid Dynamic Laboratory (GFDL) and Oregon State University (OSU). For contemporary climate at 312.5 ppmv CO₂, TEM estimates that China has an annual NPP of 3,653 TgC/yr (10^12 gC/yr). Temperate broadleaf evergreen forest is the most productive biome and accounts for the largest portion of annual NPP in China. The spatial pattern of NPP is closely correlated to the spatial distributions of precipitation and temperature.Annual NPP of China is sensitive to changes in CO₂ and climate. At the continental scale, annual NPP of China increases by 6.0% (219 TgC/yr) for elevated CO₂ only (519 ppmv CO₂). For climate change with no change in CO₂, the response of annual NPP ranges from a decrease of 1.5% (54.8 TgC/yr) for the GISS climate to an increase of 8.4% (306.9 TgC/yr) for the GFDL-q climate. For climate change at 519 ppmv CO₂, annual NPP of China increases substantially, ranging from 18.7% (683 TgC/yr) for the GISS climate to 23.3% (851 TgC/yr) for the GFDL-q climate. Spatially, the responses of annual NPP to changes in climate and CO₂ vary considerably within a GCM climate. Differences among the three GCM climates used in the study cause large differences in the geographical distribution of NPP responses to projected climate changes. The interaction between elevated CO₂ and climate change plays an important role in the overall response of NPP to climate change at 519 ppmv CO₂. / Includes bibliographical references (p. 14-17). / Abstract in HTML and technical report in HTML and PDF available on the Massachusetts Institute of Technology Joint Program on the Science and Policy of Global Change website (http://mit.edu/globalchange/www/). / Supported by the National Aeronautics and Space Administration's Earth Observing System. NAGW-2669. Supported by the Dept. of Energy's National Institute for Global Environmental Change. 901214-HAR Supported by the Joint Program on Science and Policy of Global Change at MIT. CE-S-462041

This qualitative research maps multiliteracies onto the pedagogy of teachers of kindergarten through grade 12. It examines how teachers ready their students to become multiliterate beings, that is, how teachers approach literacy in a manner that is reflective of the diversity of students in order to prepare them for their futures in a competitive digital world. Twenty teachers from Northwestern Ontario were selected using intensity sampling to participate in audio-taped interviews. The sample included three teachers from each of the elementary grades (kindergarten, primary, junior and intermediate) and eight teachers from the secondary panel (intermediate/senior). Teachers were nominated by school administrators and curriculum leaders based on a provided list of multiliteracies indicators. An interview guide was used to isolate elements of the content of multiliteracies (designing processes) and the form (situated practice, overt instruction, critical framing and transformed practice). One teacher from each of the four elementary grade divisions, as well as two teachers from the secondary level were observed and participated in follow-up interviews. Individual interviews were coded using a deductive frame as well as constant comparison. The observational field notes and follow-up interviews were used as triangulation to enrich the interview data. Excel and macros were used to organize the data. Findings document teachers’ conscious inclusions of content reflective of student subjectivities as well as the need for teachers to continue to challenge the role of literacy as more than compensatory education. Teachers’ pedagogies were rooted in engaging students and demonstrated a focus on the affective needs of students that reached beyond multiliteracies theory. Both critical literacies and information technology were integrated into pedagogy, although teachers reported feelings of low confidence and the desire for additional professional development opportunities. Other findings that emerged emphasized a range in orientations to student risk in literacy learning and strong alignments with provincial protocol. This study advances the research field by describing connections between multiliteracies as a theoretical frame and teachers’ perceptions of their literacy practices across grades K-12 and highlights ways in which multiliteracies can extend literacy pedagogy.