VictorJuiz/thesis huggingface dataset:
Linoleate deficiency in rats, measurement of carbon recycling from linoleate and a comparison with essential fatty acid deficiency

The purpose of this study was to measure the utilisation of (1-$\sp{14}$C) -linoleate in various organs during adequate dietary linoleate intake as well as during its deficiency and to draw comparisons between the states of linoleate and essential fatty acid deficiency. The accumulation of $\sp{14}$C was greater in testes, heart and carcass lipids of linoleate deficient rats with respect to controls (7-fold for testes, 10-fold for heart, 3-fold for carcass). However, carbon recycling into sterols was also greater in several tissues of linoleate deficient rats than in controls. This indicates that even in the deficient state, carbon recycling of linoleate accounts for a significant part of linoleate metabolism. A comparison of several indices of classical essential fatty acid deficiency between linoleate deficiency and previous studies involving essential fatty acid deficiency indicate that the degree of deficiency induced by the absence of dietary linoleate is not as severe as that observed in essential fatty acid deficiency.
Life history and sexual selection

Three of my thesis chapters use the fecundity by numbers of mates regression slope (Bateman slopes) to understand how life history allocation patterns can influence the strength of sexual selection. Males may typically experience stronger sexual selection because the Bateman slope is larger for males than for females. In fact, the ratio of male over female slopes is a way of quantifying sexual conflict over mating frequency. This conflict may explain the typically higher male motivation to remate relative to females, as well as most other sexual differences (e.g., showiness of peacocks). Animals can allocate energy to different aspects of their life history, and how this allocation affects the strength of sexual selection is the central question of most of my thesis. Chapter 2 develops a model for how sexual selection can be affected by particular life history allocation patterns. I focus on reversals in the strength of sexual selection (e.g. females compete for mates), using Bateman slopes for translating changes in allocation to mating effort into changes in the strength of sexual selection. My third and fourth empirical chapters test predictions (from Chapter 2) about how the upper limit on sexual selection differs for males and females. Chapter 3 quantifies the effects of a life history trade-off (between having functional wings and fecundity) on sexual differences in these upper limits. Chapter 4 tests predictions about the relationship between the male and female upper limits and the potential for sexual conflict over mating frequency. This chapter also examines why the male upper limit is not greater than the female upper limit as expected. The last two chapters of my thesis are theoretical and do not involve Bateman slopes. Chapter 5 estimates the statistical power of a test designed to ask whether two traits are evolving in a correlated way across a phylogenetic tree. Chapter 6 contains an analytical model of the forces that can cause sexual selection on females to increase. The model examines how the potential sterility of male mates, or less costly risks like mates with sex-ratio distorters, can cause sexual selection for multiple mating in females.
Cognitive aspects of restraint, situational and task influences on memory for body shape-related information in dieters and non-dieters

It has been proposed that individuals who regard body shape and weight as important aspects of the self will display "schematic processing" for body shape- and weight-related information (Markus, 1977; Markus, Hamill, & Sentis, 1987). Based on this theory, it was predicted that dieters, a group highly concerned with body shape and weight, would display memory bias for body shape-related information whereas non-dieters would not. Four studies were conducted to examine memory bias for body shape stimuli, as well as task and situational factors that may influence this process in dieters and non-dieters. Study 1 examined the effect of a milkshake priming manipulation on implicit and explicit memory for body shape stimuli. Both dieters and non-dieters displayed an explicit memory bias for body shape words relative to neutral words and non-dieters displayed poorer implicit memory for body shape words relative to neutral words. The milkshake had no effect on memory. Study 2 investigated the relation between attentional bias and memory bias. Dieters did not display an attentional bias for body shape words on a modified Stroop task, but did display a significant attentional bias for fat words on a word reading task. Both dieters and non-dieters displayed an explicit memory bias for body shape words. Study 3 extended Studies 1 and 2 by examining the effect of the body shape of the experimenter on memory for body shape words, as measured by a more effortful memory task (i.e., free recall). Manipulation of the experimenter's body shape served to prime body shape and weight thoughts. With an average-weight experimenter, dieters displayed a memory bias for body shape words; in contrast, non-dieters did not exhibit any memory bias. With an underweight or overweight experimenter, the non-dieters resembled the dieters in the average-weight experimenter condition, displaying a memory bias for body shape words. Study 4 investigated an interactional theory of memory bias looking at the influence of an environmental factor (priming by weight and shape questionnaires) and the nature and level of the encoding task on memory for body shape words. Surprisingly, the priming manipulation had no effect on memory. However, both the nature and level of encoding interacted with dieting status to produce memory bias for body shape stimuli. It was concluded that dieters are in a state of chronic activation with respect to body shape and weight thoughts. Dieters consistently displayed a memory bias for body shape stimuli and were not greatly influenced by priming manipulations. In contrast, whether non-dieters will display a memory bias for body shape stimuli is highly dependent on their weight and shape thoughts being activated by a priming event.
Sensitivity and specificity of screening for pulmonary arteriovenous malformations

'Objective'. To determine sensitivity and specificity of contrast echocardiography (CE) for diagnosing pulmonary arteriovenous malformations (AVMs) in Hereditary Hemorrhagic Telangiectasia (HHT). 'Methods'. 143/164 (87%) consecutive patients seen between 98-02-01 and 99-10-31 at the Toronto HHT Clinic underwent CE, oxygen shunt test (OST) and chest radiography (CXR). Patients with positive screening underwent pulmonary angiography (gold standard). 'Results'. Sensitivity and specificity of CE were 93% and 40%, when verification bias ignored. CE was more sensitive than OST (p = 0.0006) and CXR (p = 0.0001), but less specific than CXR (p = 0.0008). Using logistic regression to impute data for unverified patients, sensitivity and specificity were both 79%. Using novel scenario analysis to address verification bias, the possible range of sensitivity was 34-94% and specificity was 29-84%. 'Conclusion'. CE is more sensitive than conventional screening tests for pulmonary AVMs in HHT, when verification bias ignored. However, verification bias effects on estimates of sensitivity and specificity may be large.
CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand

4-1BBL is a member of the tumour necrosis factor (TNF) family expressed on activated antigen presenting cells. I have produced a soluble form of 4-1BBL using the baculovirus expression system. When co-immobilized on plastic with anti-CD3, soluble 4-1BBL induces IL-2 production by resting CD28$\sp+$ or CD28$\sp-$ T cells. 4-1BBL is inferior to anti-CD28 in T cell activation at low concentrations of anti-CD3. However, when 4-1BBL is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in the stimulation of IL-2 production by resting T cells. In order to examine the functional role of TNF receptor associated factor 2 (TRAF2) in 4-1BB signaling, resting T cells isolated from TRAF2-deficient mice were used and failed to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.
Structural and functional studies of the glucagon-like peptide-1 (GLP-1) receptor

GLP-1 is now being considered as a new treatment for Type 2 diabetes. The requirements, however, for ligand binding and activation to the GLP-1 receptor are currently unknown. A c-myc/his epitope tagged N-terminal GLP-1 receptor domain (Nt GLP-1 Rc) and a V5/his epitope tagged GLP-1 receptor was expressed in Sf9 cells. Cross-linking studies revealed a direct physical interaction between $\sp{125}$I-GLP-1 (7-36)NH$\sb2$ and Nt GLP-1 Rc implicating this region in ligand binding. To gain an understanding of ligand-receptor interaction, modified GLP-1 peptides were assessed for their ability to interact. Glutamate at position 3 and glycine at position 4 were crucial for receptor activation. The C-terminal region was essential for receptor binding. In conclusion, our studies suggest that Nt GLP-1 Rc interacts with the C-terminal region of GLP-1. The structure-function studies of the GLP-1 receptor and its ligand could aid in the design of potential GLP-1 analogues for future NIDDM therapy.
Structure and function of the human insulin receptor, quaternary 3D reconstruction of the insulin-insulin receptor complex and the structural localization of the insulin-binding site

The elucidation of the mechanism of cellular signal transduction is one of the key challenges in biology. The first step in this pathway has been particularly refractory to study. In the case of insulin action, it is the binding of insulin to its cell surface receptor, a large integral transmembrane glycoprotein. The binding of insulin results in the activation of the cytoplasmic domain of the receptor as a tyrosine kinase. While much is known about the interaction of the activated receptor with its substrates leading to downstream signal transduction, how the binding of insulin to the extracellular domain of the receptor can lead to receptor activation remains unknown. The specific goal of this study is to localize the insulin-binding site of the insulin receptor (IR), and, if possible, to elucidate in molecular details the insulin-IR interaction and the structure-function relationship of the insulin receptor. To achieve this goal with biochemical approach, I used the baculovirus expression system to produce in large quantity the extracellular domain of the human insulin receptor, and used various specific photoaffinity probes to identify the insulin-contacting sites. Peptide identification methods of high sensitivity were developed to detect the labeled IR fragment containing the putative insulin-binding site by HPLC peptide mapping analysis. A small fragment of 1-3 kDa that might contain the putative insulin-binding or contacting site on the receptor Ã subunit was detected. However, partly due to the lack of an insulin photoprobe with a high efficiency of cross-linking, and a high efficiency peptide mapping method, I failed to obtain a sufficient quantity of the fragment for amino acid sequencing. In an alternative approach, using gold-labeled insulin as a ligand, and sets of electron micrographs obtained by low-dose low temperature dark field scanning transmission electron microscopy (STEM) of the insulin-IR complex, I successfully reconstructed the 3D quaternary structure of the whole 480-kDa human insulin receptor (HIR), complexed with insulin, at a resolution of 20 Å. Contiguous high densities within the 3D structure indicated a two-fold symmetry for this dimeric receptor and the presence of subdomain structures which begin with the extracellular subdomain involved in insulin binding and terminate with the intracellular tyrosine kinase subdomains. These subdomains were confirmed by fitting known high-resolution crystal domain substructures. In addition, the 3D insulin-HIR complex provides evidence for the involvement of only a single insulin molecule in receptor activation. It also explains many of the known characteristics of insulin binding to its receptor and many biochemical findings in the studies of the insulin receptor.
Communicative ethics, developing a practical procedure of discourse

Jurgen Habermas presents a theory of discourse ethics which is a conflict resolution theory based on a process of moral argumentation. To move discourse ethics beyond a purely theoretical venue, Habermas introduces Lawrence Kohlberg's cognitive model of moral development. In turn, Seyla Benhabib questions Habermas' version of discourse ethics by examining the theory and model which she sees to be grounded on a rationalist methodology that is shared by both Habermas and Kohlberg. Using Benhabib's insights, I reexamine Kohlberg's idea of the moral domain and argue that Kohlberg actually supports Benhabib's analysis, and can even be seen to expand it. As a result, we are left with a solid theory of discourse ethics, whereby both Kohlberg and Benhabib can be seen to contribute to Habermas' account. While they maintain the foundations of Habermas' discourse ethics theory, they reformulate the moral domain to accommodate a practical and viable account of moral decision making.
Average case reductions for subset-sum and decoding of linear codes

In a 1996 paper, R. Impagliazzo and M. Naor show two average case reductions for the Subset Sum problem (SS). We use similar ideas to obtain stronger and additional such reductions for SS. Furthermore, we use modifications of these ideas to obtain similar reductions for the Decoding of Linear Codes problem (DLC). The theorems give further evidence that the hardest case for Average case SS is when the number of integers is equal to their length. For Average case DLC, the theorems give evidence that the hardest case is when the dimension of the code is equal to the channel capacity times the length of the words. Average case SS and DLC hardness assumptions can be used to obtain one-way functions, pseudorandom generators, and secure private-key cryptography.
The fate of microspheres in the ovine pulmonary microcirculation

Microspheres are microscopic polymer beads used therapeutically for drug delivery and in research to measure or obstruct blood flow. In studies of blood flow obstruction, it is assumed that microspheres obstruct and remain in the lumen of blood vessels. Recent evidence indicates that obstruction of ovine, umbilical arterioles with microspheres may be transient; however, the mechanism by which obstruction is resolved is unclear. This is the first study to attempt to elucidate this mechanism. Following infusions of polystyrene microspheres into the lungs of lambs, microspheres were found outside of blood vessels and endothelial cells were found on the surface of these microspheres. This finding indicates that biodegradable microspheres can be used to deliver drugs to the perivascular area. Microspheres with autologous, DNA-tagged, carotid endothelial cells cultured onto them were infused into the lungs of lambs. Tagged cells were found in the vicinity of the microspheres at 4 days but not 21 days. This finding suggests that microspheres may be potential cell delivery vehicles for vascular gene therapy, if cell viability can be enhanced.
The fate of microencapsulated rat islets transplanted into diabetic mice

The fate of encapsulated rat islets transplanted into diabetic mice was investigated. Islets of Langerhans isolated from male Wistar rats were encapsulated in alginate-polylysine-alginate membranes. One thousand microencapsulated islets were transplanted into the intraperitoneal cavity of STZ-induced diabetic mice. All mice became normoglycemic at day one posttransplantation and maintained normoglycemia throughout the study. At 3, 7, and 14 days posttransplantation the encapsulated islets were recovered from the transplant recipients and analyzed for: insulin content, insulin secretion, apoptosis, and morphological changes. Results indicate a significant decrease (p $<$ 0.0001) in insulin content and insulin secretion in the retrieved islets over time. By day 14 posttransplantation there was no significant difference (p $>$ 0.3) in the amount of apoptosis occurring in the transplanted islets as compared to pre-transplantation values. It is evident the in vivo environment may be favourable for islets survival. Further research must be undertaken to completely determine the fate of microencapsulated islets.
Behavior of a random copolymer at the interface between two immiscible solvents

A self-avoiding walk model of copolymer localisation between two solvents is developed which allows the interaction between comonomers and solvents to be tuned independently of one another. Elements of the form of the two-dimensional phase diagram parametrised by the interaction energies in each phase are predicted by rigorous analysis. Exact enumeration of walks on the simple cubic lattice up to 'n' = 20 and series analysis allow the location of phase boundaries in the diagram to be estimated. The random copolymer adsorption model is also studied giving the location of the adsorption transition in this system and new estimates of critical exponents for terminally attached walks are determined by series analysis up to 'n' = 20.
Relationship between polarographic oxygen measurements, metastatic ability and EF5 binding in murine tumour models

Hypoxia exists in most solid tumours. There is data to support that it is implicated in resistance to radiotherapy and chemotherapy and might contribute to tumour aggressiveness and metastasis. Therefore, methods that measure hypoxia are of significant interest. In this thesis the relationship between tumour oxygenation, as measured with the Eppendorf pO2 Histograph and metastatic ability was examined in two rodent tumour models, KHT-C and SCC-VII. A significant increase in early pulmonary metastasis formation was observed in hypoxic KHT-C tumours. A similar trend was observed in SCC-VII tumours but it was not statistically significant. In addition, a comparison was made between the Eppendorf technique for measuring hypoxia and labelling of hypoxic cells using the marker EF5 in two human cervix cancer xenograft models, Me180 and HeLa. In Me180 tumours, a significant correlation was found between the two techniques but no correlation was found in HeLa tumours. It was hypothesised that histopathological characteristics such as extensive necrosis might have contributed to the disparate results.
Modification of human hemoglobin with dibromosalicyl esters of benzene di, tri, and tetra carboxylates

Specific anchoring of biologically active molecules to human Hb A can be accomplished by using affinity labeling reagents targeting the cationic sites in Hb. Derivatives of d-biotin, isoleucyl-glycine and phenylalanine have been designed and synthesized for anchoring to hemoglobin. These reagents bind to, and subsequently react at specific sites to give stable, cross-linked hemoglobin conjugates. Major reaction products were isolated and structurally characterized by HPLC-MS, SDS-PAGE and proteolytic digestion. The major modified components consisted of hemoglobin cross-linked between the Lys-82 residues of each $\beta$ chain and Lys-99 of each $\alpha$ chain. Applications of this methodology may include introduction of novel biological properties on hemoglobin by means of biotin-avidin-biotin bridges and use of hemoglobin as a mean for transport and delivery of organic substances such as peptides which are difficult to develop as pharmaceuticals due to their short half-lives.
Observer agreement in histopathological evaluation of oral epithelial dysplasia

'Objectives'. We studied observer agreement in diagnosing oral epithelial dysplasia, (OED). 'Methods'. Sixty-four slides were each examined twice by three oral pathologists. Information provided for each observation was altered in 50% of second examinations. The modal diagnosis was used as a gold standard to assess conformity. 'Results'. Pairwise interobserver weighted kappa (Kw) ranged from 0.68-0.83 with a group Kw of 0.74. Intraobserver Kw ranged from 0.82-0.96. Using a 3 point ordinal scale decreased Kw levels. Category specific simple kappa for normal, mild, moderate, severe and carcinoma-in-situ (CIS) were 0.51, 0.24, 0.26, 0.30, and 0.57. Information changing observer expectation significantly influenced diagnosis. 'Conclusions'. There was substantial interobserver consistency and almost perfect conformity when diagnosing OED. Agreement was best with CIS and lowest with mild dysplasia, cases. Observer bias was present; consensus and calibration exercises may be appropriate. The full 5 point ordinal scale was best when assessing OED. Referring clinicians should include accurate patient information with specimens.
Contextualizing patient-doctor relationships in Singapore

My inquiry examines the disjuncture between experiences of people with diabetes and biomedical discourses that support global capitalism within the two-tiered biomedically-based health system in Singapore. I use an institutional ethnographic approach, which is both a method of inquiry and an analytical process, to explore bow relations of ruling are reproduced in specific relations between physicians and people with diabetes. As a subtext, I produced a critical autoethnography that critiqued my original research plans. My inquiry documents the lived experiences of people with diabetes through interview transcripts (describing physicians), relevant texts (including historical and present political practices), fieldnotes of over three years as a participant observer within the Diabetic Support Group of Singapore (DSGS) and a journal of my Canadian expatriate experiences. Diabetes is part and parcel of Singapore's economic 'miracle' and the adoption of consumerism. People with diabetes experience a bifurcation of consciousness as it is challenging to comply with the government ideology of hard work while simultaneously following a 'healthy' diabetic regimen. Singapore's local health care policies impose Western biomedicine within a two tiered system in which 80 percent of the population attend private for-profit clinics. Indigenous health practices are marginalized. A fiscal orientation inherent to contemporary global economics can be seen within patient-doctor interactions. For example, physicians are increasingly concerned about the accounting aspect of their profession and most people with diabetes tacitly accept this 'revolving door' efficiency. Members of the DSGS, a support group for insulin-dependent diabetic families, express dissatisfaction with existing physician services while health professionals associated with the group tend to critique other aspects of the system. Rather than rejecting the biomedical health care system itself, group members claimed friendship and diabetic education as primary reasons for their attendance. A Freirian dialogue can be seen to be part of the social process of this group. However, from a critical feminist perspective, the DSGS can also be seen as responding to external social forces. That is, it has undertaken the least revenue-generating health work of psychosocial support and patient education thus salvaging biomedicine and smoothing the transition to consumerism in medicine.