In my dissertation, I examine the works of six writers (George S. Kaufman, Moss Hart, Clarice and Elisa Lispector, Evgenia Ginzburg and Vasilii Aksyonov) who did not explore their Jewish identity in their texts and were subsequently left out of the canons of Jewish literature in their respective countries. My goal is to recalibrate the concept of the Jewish canon from the charged notion of identity to a theory of shared thematic material in which the works of hyphenated Jewish writers will be considered under the category of ‘Jewish American, Brazilian, or Russian’ if they share definite attributes. This was a transnational study showing that similar forces were at work not only in one country, but across continents, affecting the sensibilities of Jewish writers in remarkably similar ways. On a larger scale their de-thematized narratives share thematic tropes and belong to a ‘minor, liminal, marginal narrative,’ a narrative which attempted to work within the scope of the master narratives produced by the hegemonic culture. I have claimed that even though these six writers did not thematize identity in their texts, because of the negative political and social situation for the Jew in the first half of the twentieth century in western civilization, this situation and the writers’ own alterity produced similar and overlapping narratives. / text

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease which currently lacks rapid and definitive diagnostic tests. Recently identified neuron specific splice variant molecules, Per28 and NFL-60, have been shown to contain unique epitopes and to have altered levels of expression in ALS patients. It is believed that these factors make Per28 and NFL-60 excellent candidate biomarkers for the ALS disease state. In this study, we attempted to develop ELISA assays directed against Per28 and NFL-60, as well as a generalized guideline for splice variant ELISA development, which could be used in a clinical setting. Limitations in currently identified antibodies to the splice variants allowed only for the completion of a Per28 ELISA, which lacked the sensitivity for clinical relevance. This assay creation process, however, did produce a guideline for similar ELISA development, which should allow for the more expeditious creation future ELISA.

<p>This study shows that herbs can be effectively screened for potiential bio-activity using in vitro methods. Further studies will be needed to better explore Artemisia afra&rsquo / s effect on immunoregulation, particularly long term effects of the herb on the immune system and its effect on other disease states.</p>

B cells have a central role in the pathogenesis of collagen-induced arthritis (CIA), an animal model of the autoimmune disease rheumatoid arthritis. In this report, a specific subset of an innate type of B cells, B-1 B cells, have been studied for the involvement in CIA. The B-1 B cells were shown to produce small amounts of collagen-specific antibodies upon stimulation in vitro, suggesting that they play a minor role in the development of CIA. This report also includes how marginal zone B cells, another innate type of B cells with natural collagen-reactivity, can be identified in the medullary sinuses of lymph nodes of collagen-immunized mice, implying involvement in auto antigen trapping.

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease which currently lacks rapid and definitive diagnostic tests. Recently identified neuron specific splice variant molecules, Per28 and NFL-60, have been shown to contain unique epitopes and to have altered levels of expression in ALS patients. It is believed that these factors make Per28 and NFL-60 excellent candidate biomarkers for the ALS disease state. In this study, we attempted to develop ELISA assays directed against Per28 and NFL-60, as well as a generalized guideline for splice variant ELISA development, which could be used in a clinical setting. Limitations in currently identified antibodies to the splice variants allowed only for the completion of a Per28 ELISA, which lacked the sensitivity for clinical relevance. This assay creation process, however, did produce a guideline for similar ELISA development, which should allow for the more expeditious creation future ELISA.

Die Protothekenmastitis des Rindes ist eine therapieresistente, weltweit vorkommende Infektionskrankheit. Das ätiologische Agens, die farblose Alge Prototheca (P.) zopfii, kommt ubiquitär in feuchten Habitaten vor und verursacht fakultativ akute bis chronische Entzündungen des Rindereuters. Es gibt Hinweise auf das Vorkommen eines speziellen, Mastitis-assoziierten Biotyps von P. zopfii, der sogenannten Variante II. Durch die oft zu beobachtende endemische Ausbreitung in Milchviehbeständen sowie durch die nachhaltige Therapieresistenz, welche oft zum wirtschaftlichen Totalverlust der betroffenen Milchkühe führt, stellen Protothekenmastitiden beim Rind ein großes ökonomisches Problem für den betroffenen Betrieb dar. Da bisher nur sehr beschränkte Erkenntnisse zur lokalen und systemischen Immunantwort sowie zur Erregerausscheidung im Verlaufe der Protothekenmastitis des Rindes vorlagen, wurden die verschiedenen klinischen Stadien dieser Infektion serologisch, kulturell sowie durch Bestimmung der Zahl der somatischen Zellen in der Milch charakterisiert. Zu diesem Zwecke wurden drei verschiedene ELISA-Systeme entwickelt, die anschließend auch auf ihren möglichen Einsatz bei der Diagnostik der Protothekenmastitis hin untersucht wurden. Dies geschah in einem hochgradig an Protothekenmastitis erkrankten Milchviehbestand. Darüber hinaus wurden verschiedene Isolate von P. zopfii auxanographisch, biochemisch, serologisch und genetisch untersucht, um eine Differenzierung innerhalb der Algenspezies P. zopfii vornehmen zu können. Anhand der auxanographischen, biochemischen, serologischen und genetischen Untersuchungen war eine eindeutige Differenzierung von drei verschiedenen Bio-, Sero- und Genotypen innerhalb der Algenspezies P. zopfii möglich. Alle untersuchten Mastitisisolate konnten eindeutig der Variante II von P. zopfii zugeordnet werden, womit dieser Variante eine besondere epidemiologische Bedeutung bei der Entstehung der Protothekenmastitis des Rindes zu zukommen scheint. Die Untersuchungen dieser Arbeit zeigen, dass akut infizierte Tiere sowohl die höchsten Antikörperaktivitäten an IgG im Blutserum sowie an IgA und IgG1 im Milchserum als auch die höchsten Gehalte an somatischen Zellen in der Milch aufweisen. Chronisch infizierte Milchkühe weisen zum Teil sehr hohe Antikörperaktivitäten in der Milch auf und unterschieden sich nicht signifikant von akut infizierten Tieren. Demgegenüber weisen diese chronisch infizierten Tiere signifikant höhere IgG-Aktivitäten im Blutserum sowie IgA- und IgG1-Aktivitäten in der Milch auf als nicht infizierte Tiere. Somit ist eine eindeutige Differenzierung zwischen infizierten und nichtinfizierten Kühen möglich. Die ELISAs zum Nachweis von spezifischem IgA und IgG1 im Milchserum erwiesen sich als besonders geeignet, um infizierte Kühe zu identifizieren. Beide serologischen Testsysteme wiesen Sensitivitäten von 96,3 % für IgA sowie 92,6 % für IgG1 und Spezifitäten von 94,4 % (IgA) und 96,3 % (IgG1) auf. Demgegenüber wies der ELISA zum Nachweis von spezifischem IgG im Blutserum bei einer Spezifität von 100 % nur eine Sensitivität von 81,5 % auf. Die sehr gute Reproduzierbarkeit der Tests wurde durch Intra-Assay-Variationen von 6,08 % für den Nachweis von IgA im Milchserum und 7,20 % für IgG1 sowie durch die geringe Inter-Assay-Variation von 6,32 % (IgA) und 9,74 % (IgG1) belegt. Der Einsatz dieser Testsysteme bei der Sanierung eines hochgradig mit P. zopfii infizierten Milchviehbestandes zeigte, dass die serologische Diagnostik dem bisher gebräuchlichen kulturellen Erregernachweis bei der Identifikation intermittierender Erregerausscheider überlegen ist. Es wurde deutlich, dass 70,5% der infizierten Tiere die Erreger über einen Zeitraum von 12 Monaten permanent ausschieden und mindestens weitere 4,9 %, wahrscheinlich jedoch wesentlich mehr, dieser infizierten Tiere intermittierende Erregerausscheider waren. Somit scheint der serologische Erregernachweis für die Diagnostik der Protothekenmastitis des Rindes besser geeignet zu sein als die kulturelle Diagnostik. Dabei wurde die höchste Sensitivität durch die Kombination des Nachweises von spezifischem IgA und IgG1 im Milchserum erzielt. / Protothecosis is a severe, often endemic mastitis in cattle caused by colorless algae of the genus Prototheca. Only little and insufficient knowledge about the organism itself, and the host immune response to this infection existed. Therefore, the aim of this thesis was to characterize the local and systemic immune response and the possible elimination or persistence of the pathogen in the host. To gain more information on the specific immune response, different clinical stages of infection were characterized serologically, culturally, and by determination of the number of the somatic cells in milk. Three different ELISA systems were developed, which were also examined for their diagnostic application potential. For the investigations, a dairy herd highly infected with Prototheca zopfii and severe clinical manifestation of protothecal mastitis was used. The ELISA was evaluated using serum and whey from animals with different clinical stages of infection. As antibody isotypes, IgG in serum, and IgA and IgG1 in whey were used. In addition, different isolates of P. zopfii were biochemically, serologically, and genetically examined in order to allow a differentiation of individual isolates within the species P. zopfii. The biochemical, serological and genetic investigations allowed a clear differentiation of the three known Variants of P. zopfii. All examined mastitis isolates could be assigned to variant II of P. zopfii. Therefore, it can be concluded that this variant has a particular epidemiological significance in the etiology of bovine protothecal mastitis. The serological investigations showed high antibody activities during acute and chronic stage of infection. The antibody activity was low in chronically infected, but presently cultural negative animals and also in uninfected animals. A strong correlation was observed between whey IgA and whey IgG1 antibody activity and the count of somatic cells in milk. Whereas, only a weak correlation exists to the number of algae cells excreted with the milk. A sensitivity of 96 % and a specificity of 94 % were calculated for the ELISA based on IgA levels. The ELISA for detection of specific IgG1 in whey shows a sensitivity of 92,6 % and a specificity of 96,3 %. Intra-assay and interassay variations were calculated to be at 6.08 % and 6.32 %, respectively. Based on these data, these ELISAs are suitable for discrimination between infected and uninfected animals, and might therefore be used for the screening of affected herds. When used in the remediation of a high-grade infected dairy herd the serological showed clear advantages in the identification of intermittent shedders. By culturing of Prototheca from milk, it was shown that 70.5% of the infected animals were permanent shedders, whereas 4.9 % were intermittent shedders. Since intermittent shedders could be clearly identified serologically, but might not be recognized by culturing, it can be assumed that serological diagnostics is more suitable for the identification of inapparently infected, intermittent shedders.

El NFAT5 es un factor de transcripción de la familia Rel, la cual incluye a los NFATc y los NF-[kappa]B. Hasta ahora, el NFAT5 había sido caracterizado principalmente como un factor de respuesta a estrés osmótico ya que regula la expresión de genes osmoprotectores y citoquinas en respuesta a hipertonicidad. En este trabajo hemos identificado y caracterizado una nueva función del NFAT5, la regulación de genes (TNF[alfa], IL6, iNOS) activados por la vía de los receptores de tipo Toll (TLR), importantes para la respuesta inmunitaria innata y adaptativa a una amplia variedad de estímulos patogénicos. Nuestros resultados muestran que el NFAT5 es un regulador importante en la ruta de los TLR, jugando un papel en la actividad de varios miembros de esta familia de receptores, tal y como lo hacen los factores de transcripción NF[kappa]B e IRF5. / NFAT5 is a transcription factor of the Rel family, which includes NFATc and NF-[kappa]B. NFAT5 has been mainly characterized as a hypertonicity responsive factor, since it regulates the expression of osmoprotective genes and cytokines in response to osmotic stress. In this work we have identified and characterized a novel role for NFAT5, the regulation of genes (TNF[alfa], IL6, iNOS) activated by the Toll-like receptor pathway (TLR), important for innate and adaptive immunity responses to a wide variety of pathogenic molecules. Our results show that NFAT5 is an important transcription factor of the TLR pathway, playing a role in the activity of several members of this receptor family, like other transcription factors such as NF-[kappa]B and IRF5.

[pt] Esta pesquisa partiu das leituras da obra de Elisa Lispector e da seguinte indagação do pesquisador: por que Elisa, publicada, considerada pela crítica e premiada na segunda metade do século XX no Brasil, caiu no esquecimento? A proposta é resgatar os motivos de interesse do trabalho da escritora. Dentre tais motivos, destacam-se -- em construção autônoma, mas inter-relacionada -- a busca da memória de uma família judaica expatriada, que fugiu da Ucrânia para o Brasil, e o questionamento constante da identidade e das relações interpessoais no contexto da dimensão temporal. As personagens, quer evidenciem ou não traços (auto)biográficos, delineiam-se, ao longo dos contos e romances, sempre empenhadas na construção de sua subjetividade. A tarefa projetada desenvolveu-se com o apoio das entrevistas feitas pelo autor da dissertação e de sua coleção de críticas referentes aos livros de Elisa, desenhos e pinturas do seu acervo, bem como fotos da família Lispector. O enfoque da situação da escritora e de sua obra teve, como principal referência teórica, os princípios da crítica biográfica, orientando não apenas a leitura de registros da vida de Elisa em contraponto à análise de amostras escolhidas de seus escritos, como também a inserção das experiências do pesquisador para a construção da figura da escritora. O objetivo maior é evidenciar a importância do resgate da obra de Elisa Lispector para a literatura brasileira. / [en] This research started from readings of Elisa Lispector and the question: why has her work, published, well regarded by critics and awarded prizes in the second half of the twentieth century in Brazil, fallen into neglect? The idea is to highlight the points of interest in Lispector s work. Foremost among these are the following (each a good reason in its own right, but all interconnected): the memories of an expatriate Jewish family who fled Ukraine for Brazil, and the constant questioning of identity and interpersonal relations over time. The characters—whether or not they contain (auto) biographical features—in her short stories and novels are always involved with the construction of their own subjectivity. This study relied on the interviews made by the author and on his collection of criticism related to Elisa Lispector s books, drawings and paintings belonging to her, as well as photographs of the Lispector family. The basic theoretical underpinnings of this study of a writer s life and work are the principles of biographical criticism. They provide guidelines not only for the reading of the records of a writer s life in the light of analyses of samples chosen from her writings, but also for an understanding of the researcher s own experiences in his construction of the figure of Elisa Lispector. The major goal here is to underscore the importance of rediscovering her work for Brazilian literature.