This thesis investigates Spinoza's mind-body theory starting with the discussion of the diverse interpretations of his mind-body theory such as hylomorphism, idealism, epiphenomenalism, and materialism. From the critical comments on inadequacies of these interpretations, it turns out that Spinoza's argument of the relationship between the mind and the body should be understood as holding that there is a non-causal relationship between the mind and the body and that they have equal weight. Although the parallelistic interpretation is compatible with the above understandings, we cannot ascribe traditional parallelism to Spinoza. His parallelism is derived from his argument of identity between the mind and the body, which is based on his substance monism and attribute dualism. We should therefore understand Spinoza's mind-body theory as an identity theory which leads to a parallel relationship between the mind and the body. Since the double aspect theory argues both identity and parallelism between the mind and the body, the doctrine we should ascribe to Spinoza is the double aspect theory. Furthermore, owing to the fact that Spinoza maintains substance monism and attribute dualism (assuming an objective view of the attributes of thought and extension, which are distinct), there is, in Spinoza's theory, an identity between mental and physical events while there is no identity between mental and physical properties: the mental and the physical events are one and the same event described under mental and physical properties, respectively. From the fact Spinoza finds identity in individuals or events, but not in properties, it follows that his theory should also be understood as a kind of token identity theory.

The aim of this thesis is to examine the educational and psychological theories of the renaissance philosopher Juan Luis Vives. A brief history of Vives' life is given as background information and, to place his work in context, the central concepts of Renaissance Humanism are explained. As Vives was influenced by Desiderius Erasmus and by the central tenets of Northern Humanism, information is given on these subjects. The main focus of the research is a study of Vives' pedagogy and psychology as set out in the texts De institutione foeminae Christianae, De tradendis disciplinis and De anima et vita. Vives' educational work is discussed in Chapters 4 and 5, and comparison is made with other renaissance theories of education. It will be explained that his educational philosophy rests upon his theory of the soul. This led him to consider such things as the role of memory in the learning process, the need to take account of children's psychological maturation when planning a course of study, and the way in which sensate information is 'translated' into percepts. Chapter 6 deals with Vives' treatise on psychological processes (De anima et vita) and includes description and analysis of his epistemology together with his examination of the 'passions' and their effect on cognitive functioning. It will be argued in Chapters 7 and 8 that aspects of Vives' work are forerunners of later theories: specifically, the philosophy of Pierre Gassendi, the study of the soul by René Descartes, and the pedagogy of John Locke. Gassendi was instrumental in reviving interest in Epicurianism and in the work of Sextus Emipricus. (DXN004,921)

B lymphocytes develop from pluripotent stem cells, and differentiate to plasma cells (PCs) in reaction to signals from the supportive microenvironment. Different sets of signals, which are derived from multiple sources such as soluble cytokines and cell-cell contacts, are required at different stages of development. For instance, murine B cell progenitors require the action of interleukin-7 (IL-7) in the early phase of their development in the bone marrow (BM). The necessity for IL-7 decreases as the cell matures, and this event is correlated with the appearance of CD22. The first two chapters of this thesis focus on the early stages of B cell development that take place in the BM. In chapter 1, I examine the IL-7 response and, although I do not show a specific role for CD22 in the loss of sensitivity to IL-7, my data suggest that cis interactions involving sialic acids might modulate the IL-7 response. This section is followed by the analysis of the effect of IL-21 on B cell progenitors in the BM. IL-21 is known to regulate the terminal stages of B cell differentiation. In collaboration with Dr. Danijela Konforte, I present evidence that B cell progenitors in the BM also express a functional IL-21 receptor and that stimulation of this receptor with IL-21 accelerates the maturation pace of B cells. I further demonstrate that proB cells stimulated with IL-21 and anti-CD40 can differentiate into immunoglobulin (Ig)-secreting cells, and discuss the possibility that IL-21 plays a role during inflammation for the development of B cell progenitors in peripheral lymphatic organs. Finally, in the last chapter, in collaboration with the laboratory of Dr. Gommerman, I investigate how the microenvironment can shape the development of B cells. It has been demonstrated by my collaborators that IgA+ PCs present in the gut produce iNOS and display traits commonly associated to the myeloid lineage, and in this chapter, I describe a co-culture system with BM and gut stroma to study the conditions that sustain the generation of IgA+iNOS+ cells. In particular, I show that the presence of microbial products is one of the key factors required for their development.

B lymphocytes develop from pluripotent stem cells, and differentiate to plasma cells (PCs) in reaction to signals from the supportive microenvironment. Different sets of signals, which are derived from multiple sources such as soluble cytokines and cell-cell contacts, are required at different stages of development. For instance, murine B cell progenitors require the action of interleukin-7 (IL-7) in the early phase of their development in the bone marrow (BM). The necessity for IL-7 decreases as the cell matures, and this event is correlated with the appearance of CD22. The first two chapters of this thesis focus on the early stages of B cell development that take place in the BM. In chapter 1, I examine the IL-7 response and, although I do not show a specific role for CD22 in the loss of sensitivity to IL-7, my data suggest that cis interactions involving sialic acids might modulate the IL-7 response. This section is followed by the analysis of the effect of IL-21 on B cell progenitors in the BM. IL-21 is known to regulate the terminal stages of B cell differentiation. In collaboration with Dr. Danijela Konforte, I present evidence that B cell progenitors in the BM also express a functional IL-21 receptor and that stimulation of this receptor with IL-21 accelerates the maturation pace of B cells. I further demonstrate that proB cells stimulated with IL-21 and anti-CD40 can differentiate into immunoglobulin (Ig)-secreting cells, and discuss the possibility that IL-21 plays a role during inflammation for the development of B cell progenitors in peripheral lymphatic organs. Finally, in the last chapter, in collaboration with the laboratory of Dr. Gommerman, I investigate how the microenvironment can shape the development of B cells. It has been demonstrated by my collaborators that IgA+ PCs present in the gut produce iNOS and display traits commonly associated to the myeloid lineage, and in this chapter, I describe a co-culture system with BM and gut stroma to study the conditions that sustain the generation of IgA+iNOS+ cells. In particular, I show that the presence of microbial products is one of the key factors required for their development.

本論文探討了以廣義線性混合模式(GLMM)結合時間及空間效果的時間空間模式，以將地區特性、人口特徵等變數，及時間變數納入模式中。有關時間效果可用B-Spline方法建構固定或隨機的時間趨勢平滑函數，而空間效果則是將各地區的隨機效果以條件自我相關模式(CAR)描述。實證部份則是應用GLMM模式分析台灣本島350個鄉鎮市區自民國八十八年到九十一年的肝癌就診資料，依性別、年齡層加以整理，並將年齡層分為0~19歲、20~39歲、40 ~59歲、60歲以上，分別代表少、青、壯、老等四個年齡層；再採用GLMMGibbs結合R軟體各個資料集分別配適時間空間模式，估計各地區之相對風險並繪製疾病地圖，據以找出各年估計的相對風險高的地區。

In this thesis we examine the method of counting BB events produced in the BaBar experiment. The original method was proposed in 2000, but improvements to track reconstruction and our understanding of the detector since that date make it appropriate to revisit the B Counting method. We propose a new set of cuts designed to minimize the sensitivity to time-varying backgrounds. We find the new method counts BB events with an associated systematic uncertainty of ±0.6%.

The human hepatitis B virus (HBV) is a small hepatotropic virus, which affects approximately 350 million chronic sufferers worldwide. It has a compact 3.2 kbp dsDNA genome encoding four major overlapping genes namely core, polymerase, surface and X required for its replication. The virus synthesises a pregenomic RNA (pgRNA) which functions both as an RNA intermediate for reverse transcription into the DNA genome and as the mRNA for the translation of the core (C) and polymerase (P) proteins. The core overlaps the polymerase gene and is translated at a 10 to 1 ratio. The polymerase gene translated from the P AUG codon is preceded by at least 4 upstream AUG codons (uAUGs), namely C AUG, C1 AUG, J AUG and C2 AUG. Various mechanisms have been implicated in the synthesis of the polymerase protein. This led to the currently accepted model which involves leaky scanning and a reinitiation mechanism in polymerase synthesis. However, multiple sequence alignment of the pgRNA revealed a short upstream open reading frame (uORF) highly conserved at the nucleotide level in all HBV subtypes and mammalian hepadnaviruses. This previously unreported uORF, designated as C0 ORF in this study is also conserved in its position and length. Past studies have either omitted this uORF in their test constructs or ignored its potential role. The C0 ORF has a conserved weak initiation context and is located within the epsilon structure within the 5� leader of the pgRNA, required for viral encapsidation. Importantly, the C0 ORF precedes and overlaps the core ORF, which may suggest an alternative model in which the core and polymerase may be translated and coordinately regulated. Fusion of the C0 ORF to luciferase showed for the first time that this uORF is translated through the detection of reporter activity (~20% of C) and also visualisation of the fusion protein via western analysis using anti-C0 and anti-luciferase antibodies. Subsequent removal of the C0 ORF implicated a role in repressing downstream core fusion protein synthesis in HepG2 cells. A similar repression was observed on J expression. To study the effect of C0 on downstream polymerase translation, a pgRNA-like DNA construct was made and subsequent mutations introduced. Mutation of the C0 AUG led to an increase in initiation at the downstream P AUG. Alteration of the existing weak initiation context to an optimal context which favours stronger initiation consistently showed a potential role for C0 ORF in facilitating reinitiation at certain downstream initiation codons including P AUG. Mutations of other uAUGs preceding the P AUG were also done to better understand their roles in regulating polymerase synthesis. The removal of the C AUG markedly increased expression from the P AUG. This study revealed other internal uAUGs in-frame to the C AUG, namely the C1 and C2 AUGs are also effectively translated, further reducing availability of translating ribosomes to downstream P AUG. Indeed the removal of the C1 and C2 AUGs led to a corresponding increase in initiation from the P AUG. Initiation at the internal J AUG was also reported and its removal showed a significant decrease in expression from the P AUG, consistent with the previous model implicating reinitiation at the P initiation site after translation of the short J ORF. The inhibitory role of the 5 uAUGs prior to the P AUG were confirmed when all were removed, giving rise to translation almost equal to that at C AUG. Taken together, these results suggest a new model in which the HBV C0 ORF plays a key role in controlling core and polymerase synthesis by repressing core translation and making available more ribosomes to downstream AUGs possibly facilitating translation reinitiation. In addition, the translation of the C0 ORF across the [epsilon] region may also preclude encapsidation, potentially acting as a switch discriminating the pgRNA template between encapsidation and translation. Therefore, the highly conserved [epsilon] region and C0 ORF present an excellent target for molecular based antiviral drugs (antisense oligonucleotides, aptamers, ribozymes) potentially providing new anti HBV drugs.

Thesis (M Nursing)--University of South Australia, 1996

Master of Science / Periodontal disease is one of the most widespread diseases in humans and is characterised by chronic gingival inflammation and B cell accumulation and resorption of the crest of alveolar bone with subsequent loss of teeth. Porphyromonas gingivalis has been identified as a putative aetiological agent for periodontitis. The aim of the research presented in this thesis was to investigate, using in vitro systems, the responses of autoreactive B-1 and B-2 cells to enterobacterial and nonenterobacterial lipopolysaccharide (LPS) to shed light on the pathogenesis of chronic periodontitis and other diseases involving B cell accumulation and autoantibody production. The hypotheses tested were: (1) B cells respond differently to enterobacterial and non-enterobacterial LPS. (2) B-1 cells are activated by a lower concentration of LPS than B-2 cells. (3) LPS stimulation results in preferential accumulation of B-1 cells. Findings consistent with these hypotheses would provide new evidence for different roles for B-1 and B-2 cells in immune responses and that LPS stimulation could lead to B-1 cell accumulation in diseases thus characterised. Initial experiments investigated the responses of representative B-1 (CH12) and B-2 (WEHI-279) cell lines to preparations of P. gingivalis and Salmonella enteritidis LPS utilising flow cytometric and quantitative molecular methods. The cell lines responded differently to the two LPS preparations. There were significant but limited effects on viability and proliferation in the WEHI-279 cell line, but no significant changes in mRNA expression levels for genes including Toll-like receptors (TLR2, TLR4, RP105), immunoglobulin (IgM), cytokines (IL-6, IL-10), co-stimulatory molecules (CD80, CD86), and regulators of apoptosis (Bcl-2, Bax). In the CH12 cell line however, LPS stimulation had greater effect. Addition of S. enteritidis LPS from a threshold level of 100ng/mL was found to rescue the cells from death, reflected by the percentage viability and proliferation. Stimulation of CH12 cells with S. enteritidis LPS also led to a decrease in expression of RP105 mRNA, which may be part of a negative feedback loop. Interestingly, stimulation with low concentrations P. gingivalis LPS appeared to inhibit proliferation but high LPS concentrations stimulated proliferation of CH12 cells, although no further significant effects were noted in other analyses. Evidence was found that CH12 cells have a high basal level of activation. This suggests that this line is constitutively activated. Stimulation with P. gingivalis or S. enteritidis LPS did not affect the level of CD80 mRNA expression. It is possible that the CH12 line constitutively expresses a maximal level of CD80 (and possibly CD86) and further stimulation will not cause any increase. Since S. enteritidis LPS appeared to have more pronounced effects on both B cell populations, this LPS was used to further investigate B cell subset responses in a mixed splenocyte culture system. Experiments examining percentage viability and number of viable cells indicated that B-1 and B-2 B cells responded differently to LPS stimulation. A threshold level for B-2 cell response (significant increase in cell number) was found to be 100ng/mL LPS, in contrast to the B-1 B cell subset which were only significantly different to the unstimulated cells when stimulated with 50μg/mL LPS. By examining the expression of CD80, the majority of murine splenic B-1 cells were found to activated prior to any LPS stimulation in vitro. In contrast, the B-2 subset showed significant increase in CD80 expression only at high (≥10μg/mL) LPS concentrations. Studies of the division index of B-1 and B-2 cells showed a significant response in both subsets following stimulation with 1μg/mL and 10μg/mL LPS. However, overall, the results are inconsistent with LPS driving the preferential accumulation of B-1 cells in disease states. These experiments provided useful evidence that supported the idea that B-1 and B-2 cells respond differently to LPS. However, these studies were unable to directly address the role of P. gingivalis LPS in periodontitis. It may be that P. gingivalis LPS could have different effects to S. enteritidis LPS on primary B cells. It is still possible that B-1 cells may be more sensitive to P. gingivalis, as opposed to S. enteritidis LPS. Studies by other groups have suggested that the TH1/TH2 profile is skewed towards TH2 in chronic periodontitis and that P. gingivalis may drive this shift via its ability to signal through TLR2 (and modulate TLR4 signalling). Further, recent studies in our laboratories have found that P. gingivalis gingipains are able to polyclonally activate B cells and to break down both IFNγ and IL-12. Future studies should further examine the effects of B-1 and B-2 interactions in the mixed lymphocyte system together with subsequent studies utilising human periodontitis biopsies. The results presented in this thesis, together with work undertaken by other investigators, suggests that LPS could perturb the normal homeostatic mechanisms of the B-1 B cell-subset and increase polyclonal activation therefore contributing to the genesis of pathologies such as chronic periodontitis.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Marco van Eijk. Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.