Showing papers by "McGill University published in 1995"

Multiple Morphologies of "Crew-Cut" Aggregates of Polystyrene-b-poly(acrylic acid) Block Copolymers.

Abstract: The observation by transmission electron microscopy of six different stable aggregate morphologies is reported for the same family of highly asymmetric polystyrene-poly-(acrylic acid) block copolymers prepared in a low molecular weight solvent system. Four of the morphologies consist of spheres, rods, lamellae, and vesicles in aqueous solution, whereas the fifth consists of simple reverse micelle-like aggregates. The sixth consists of up to micrometer-size spheres in aqueous solution that have hydrophilic surfaces and are filled with the reverse micelle-like aggregates. In addition, a needle-like solid, which is highly birefringent, is obtained on drying of aqueous solutions of the spherical micelles. This range of morphologies is believed to be unprecedented for a block copolymer system.

The garch option pricing model

Abstract: This article develops an option pricing model and its corresponding delta formula in the context of the generalized autoregressive conditional heteroskedastic (GARCH) asset return process. the development utilizes the locally risk-neutral valuation relationship (LRNVR). the LRNVR is shown to hold under certain combinations of preference and distribution assumptions. the GARCH option pricing model is capable of reflecting the changes in the conditional volatility of the underlying asset in a parsimonious manner. Numerical analyses suggest that the GARCH model may be able to explain some well-documented systematic biases associated with the Black-Scholes model.

Observation of top quark production in p̄p collisions with the collider detector at fermilab

Abstract: We establish the existence of the top quark using a $67{\mathrm{pb}}^{\ensuremath{-}1}$ data sample of $\overline{p}p$ collisions at $\sqrt{s}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1.8\mathrm{TeV}$ collected with the Collider Detector at Fermilab (CDF). Employing techniques similar to those we previously published, we observe a signal consistent with $t\overline{t}$ decay to $\mathrm{WWb}\overline{b}$, but inconsistent with the background prediction by $4.8\ensuremath{\sigma}$. Additional evidence for the top quark is provided by a peak in the reconstructed mass distribution. We measure the top quark mass to be $176\ifmmode\pm\else\textpm\fi{}8(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}10(\mathrm{syst})\mathrm{GeV}{/c}^{2}$, and the $t\overline{t}$ production cross section to be ${6.8}_{\ensuremath{-}2.4}^{+3.6}\mathrm{pb}$.

Category Theory For Computing Science

Abstract: Preliminaries. Categories. Functors. Diagrams. Naturality and Sketches. Products and Sums. Catesian Closed Categories. Finite Discrete Sketches. Limits and Colimits. More About Sketches. Fibrations. Adjoints. Algebras for Endofunctors. Toposes.

Methotrexate for the Treatment of Crohn's Disease

Abstract: Background Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are ...

Understanding Nonlinear Dynamics

Abstract: 1 Finite-Difference Equations.- 1.1 A Mythical Field.- 1.2 The Linear Finite-Difference Equation.- 1.3 Methods of Iteration.- 1.4 Nonlinear Finite-Difference Equations.- 1.5 Steady States and Their Stability.- 1.6 Cycles and Their Stability.- 1.7 Chaos.- 1.8 Quasiperiodicity.- 1 Chaos in Periodically Stimulated Heart Cells.- Sources and Notes.- Exercises.- Computer Projects.- 2 Boolean Networks and Cellular Automata.- 2.1 Elements and Networks.- 2.2 Boolean Variables, Functions, and Networks.- 2 A Lambda Bacteriophage Model.- 3 Locomotion in Salamanders.- 2.3 Boolean Functions and Biochemistry.- 2.4 Random Boolean Networks.- 2.5 Cellular Automata.- 4 Spiral Waves in Chemistry and Biology.- 2.6 Advanced Topic: Evolution and Computation.- Sources and Notes.- Exercises.- Computer Projects.- 3 Self-Similarity and Fractal Geometry.- 3.1 Describing a Tree.- 3.2 Fractals.- 3.3 Dimension.- 5 The Box-Counting Dimension.- 3.4 Statistical Self-Similarity.- 6 Self-Similarity in Time.- 3.5 Fractals and Dynamics.- 7 Random Walks and Levy Walks.- 8 Fractal Growth.- Sources and Notes.- Exercises.- Computer Projects.- 4 One-Dimensional Differential Equations.- 4.1 Basic Definitions.- 4.2 Growth and Decay.- 9 Traffic on the Internet.- 10 Open Time Histograms in Patch Clamp Experiments.- 11 Gompertz Growth of Tumors.- 4.3 Multiple Fixed Points.- 4.4 Geometrical Analysis of One-Dimensional Nonlinear Ordinary Differential Equations.- 4.5 Algebraic Analysis of Fixed Points.- 4.6 Differential Equations versus Finite-Difference Equations.- 4.7 Differential Equations with Inputs.- 12 Heart Rate Response to Sinusoid Inputs.- 4.8 Advanced Topic: Time Delays and Chaos.- 13 Nicholson's Blowflies.- Sources and Notes.- Exercises.- Computer Projects.- 5 Two-Dimensional Differential Equations.- 5.1 The Harmonic Oscillator.- 5.2 Solutions, Trajectories, and Flows.- 5.3 The Two-Dimensional Linear Ordinary Differential Equation.- 5.4 Coupled First-Order Linear Equations.- 14 Metastasis of Malignant Tumors.- 5.5 The Phase Plane.- 5.6 Local Stability Analysis of Two-Dimensional, Nonlinear Differential Equations.- 5.7 Limit Cycles and the van der Pol Oscillator.- 5.8 Finding Solutions to Nonlinear Differential Equations.- 15 Action Potentials in Nerve Cells.- 5.9 Advanced Topic: Dynamics in Three or More Dimensions.- 5.10 Advanced Topic: Poincare Index Theorem.- Sources and Notes.- Exercises.- Computer Projects.- 6 Time-Series Analysis.- 6.1 Starting with Data.- 6.2 Dynamics, Measurements, and Noise.- 16 Fluctuations in Marine Populations.- 6.3 The Mean and Standard Deviation.- 6.4 Linear Correlations.- 6.5 Power Spectrum Analysis.- 17 Daily Oscillations in Zooplankton.- 6.6 Nonlinear Dynamics and Data Analysis.- 18 Reconstructing Nerve Cell Dynamics.- 6.7 Characterizing Chaos.- 19 Predicting the Next Ice Age.- 6.8 Detecting Chaos and Nonlinearity.- 6.9 Algorithms and Answers.- Sources and Notes.- Exercises.- Computer Projects.- Appendix A A Multi-Functional Appendix.- A.1 The Straight Line.- A.2 The Quadratic Function.- A.3 The Cubic and Higher-Order Polynomials.- A.4 The Exponential Function.- A.5 Sigmoidal Functions.- A.6 The Sine and Cosine Functions.- A.7 The Gaussian (or "Normal") Distribution.- A.8 The Ellipse.- A.9 The Hyperbola.- Exercises.- Appendix B A Note on Computer Notation.- Solutions to Selected Exercises.

How scientists really reason: scientific reasoning in real-world laboratories

Abstract: In 1965 Jacques Monod and François Jacob were awarded the Nobel prize for discovering that there are regulator genes that control the activity of other genes. They discovered this by investigating the utilization of energy sources, such as glucose, in E. coli. E. coli need glucose to live and their most common source of glucose is lactose. When lactose is present, E. coli secrete betagalactosidase enzymes that break down lactose into glucose. Betagalactosidase is secreted only when lactose is present. Jacob and Monod discovered that a set of regulator genes inhibit the genes that produce betagalactosidase until betagalactosidase is needed. They proposed that there are two genes I and O that regulate the activity of the betagalactosidase producing genes and that the production of beta-gal is controlled by an inhibitory regulation mechanism. As can be seen from Figure 1, when no lactose is present the I gene produces an inhibitor that binds to the O gene, and this prevents the betagalactosidase genes from producing betagalactosidase. When Lactose is present, the inhibitor secreted by the I gene binds to the lactose, rather than the O gene. When this happens, the betagalactosidase genes are no longer inhibited and, consequently, they produce betagalactosidase. When all the lactose is used, the inhibitor again binds to the O gene and production of betagalactosidase stops. Monod and Jacob made this discovery using various mutations where the I, O, and betagalactosidase genes were mutated. Crucially, they initially thought that genetic control was due to genes switching on, or activating, other genes. It was only after a large amount of research that they discovered that the mechanism of control was inhibition. Not only was this discovery relevant to production of betagalactosidase, but it was a general model of genetic control that transformed biological research.

The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins.

Abstract: Eukaryotic translation initiation factor 4E (eIF-4E), which possesses cap-binding activity, functions in the recruitment of mRNA to polysomes as part of a three-subunit complex, eIF-4F (cap-binding complex). eIF-4E is the least abundant of all translation initiation factors and a target of growth regulatory pathways. Recently, two human cDNAs encoding novel eIF-4E-binding proteins (4E-BPs) which function as repressors of cap-dependent translation have been cloned. Their interaction with eIF-4E is negatively regulated by phosphorylation in response to cell treatment with insulin or growth factors. The present study aimed to characterize the molecular interactions between eIF-4E and the other subunits of eIF-4F and to similarly characterize the molecular interactions between eIF-4E and the 4E-BPs. A 49-amino-acid region of eIF-4 gamma, located in the N-terminal side of the site of cleavage by Picornaviridae protease 2A, was found to be sufficient for interacting with eIF-4E. Analysis of deletion mutants in this region led to the identification of a 12-amino-acid sequence conserved between mammals and Saccharomyces cerevisiae that is critical for the interaction with eIF-4E. A similar motif is found in the amino acid sequence of the 4E-BPs, and point mutations in this motif abolish the interaction with eIF-4E. These results shed light on the mechanisms of eIF-4F assembly and on the translational regulation by insulin and growth factors.

Bayesian Estimation of Disease Prevalence and the Parameters of Diagnostic Tests in the Absence of a Gold Standard

Abstract: It is common in population screening surveys or in the investigation of new diagnostic tests to have results from one or more tests investigating the same condition or disease, none of which can be considered a gold standard. For example, two methods often used in population-based surveys for estimating the prevalence of a parasitic or other infection are stool examinations and serologic testing. However, it is known that results from stool examinations generally underestimate the prevalence, while serology generally results in overestimation. Using a Bayesian approach, simultaneous inferences about the population prevalence and the sensitivity, specificity, and positive and negative predictive values of each diagnostic test are possible. The methods presented here can be applied to each test separately or to two or more tests combined. Marginal posterior densities of all parameters are estimated using the Gibbs sampler. The techniques are applied to the estimation of the prevalence of Strongyloides infection and to the investigation of the diagnostic test properties of stool examinations and serologic testing, using data from a survey of all Cambodian refugees who arrived in Montreal, Canada, during an 8-month period.

Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease.

Abstract: Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within age-matched normal control values. The effect of the apoE4 allele on cholinomimetic drug responsiveness was assessed next in a group (n = 40) of AD patients who completed a double-blind, 30-week clinical trial of the cholinesterase inhibitor tacrine. Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline. These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.

Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E.

Abstract: An important aspect of the regulation of gene expression is the modulation of translation rates in response to growth factors, hormones and mitogens. Most of this control is at the level of translation initiation. Recent studies have implicated the MAP kinase pathway in the regulation of translation by insulin and growth factors. MAP kinase phosphorylates a repressor of translation initiation [4E-binding protein (BP) 1] that binds to the mRNA 5' cap binding protein eukaryotic initiation factor (eIF)-4E and inhibits cap-dependent translation. Phosphorylation of the repressor decreases its affinity for eIF-4E, and thus relieves translational inhibition. eIF-4E forms a complex with two other polypeptides, eIF-4A and p220, that promote 40S ribosome binding to mRNA. Here, we have studied the mechanism by which 4E-BP1 inhibits translation. We show that 4E-BP1 inhibits 48S pre-initiation complex formation. Furthermore, we demonstrate that 4E-BP1 competes with p220 for binding to eIF-4E. Mutants of 4E-BP1 that are deficient in their binding to eIF-4E do not inhibit the interaction between p220 and eIF-4E, and do not repress translation. Thus, translational control by growth factors, insulin and mitogens is affected by changes in the relative affinities of 4E-BP1 and p220 for eIF-4E.

The formalin test: scoring properties of the first and second phases of the pain response in rats

Abstract: The formalin test is increasingly used as a model of injury-produced pain but there is no generally accepted method of pain rating. To examine the properties of various pain rating methods we established dose-response relations for formalin injected in the plantar surface of one hind paw, and the analgesic effects of morphine and amphetamine using the most frequently reported behavioural measures of pain (favouring, lifting, licking and flinching/shaking of the injured paw) and combinations of these. Licking, elevation and favouring of the injected paw showed a biphasic response at all formalin doses. Flinching varied in form across the time course of formalin, and the biphasic nature of the behaviour was not as apparent. In untreated rats all these behaviours were infrequent. Flinching and favouring were increased after injection of local anaesthetic into the paw but remained negligible relative to the effect of formalin. Grooming other than that directed paw was elevated in a dose-dependent manner by formalin. Intercorrelations between the behaviours were different for the initial response and the second phase. Correlational analysis indicated that no single behavioural measure was a strong predictor of formalin, morphine and amphetamine dose. A simple sum of time spent licking plus elevating the paw, or the weighted pain score of Dubuisson and Dennis (1977), were superior to any single measure (r ranging from 0.75 to 0.86). Addition of flinching and favouring to the combined pain score using multiple regression did not increase variance explained. Depending on the measure used, a sedative dose of pentobarbital produced apparent analgesia, hyperalgesia or no effect. The interphase depression of pain, as well as the analgesic effects of morphine and amphetamine, were all associated with increased motor activation. Power analysis indicated that using a moderate dose of formalin and a combined pain score gave the greatest power to detect differences in pain. It was also found that pain scores increase with ambient temperature and that rat strains may differ in formalin pain sensitivity.

Shapes, shocks, and deformations I: the components of two-dimensional shape and the reaction-diffusion space

Abstract: We undertake to develop a general theory of two-dimensional shape by elucidating several principles which any such theory should meet. The principles are organized around two basic intuitions: first, if a boundary were changed only slightly, then, in general, its shape would change only slightly. This leads us to propose an operational theory of shape based on incremental contour deformations. The second intuition is that not all contours are shapes, but rather only those that can enclose “physical” material. A theory of contour deformation is derived from these principles, based on abstract conservation principles and Hamilton-Jacobi theory. These principles are based on the work of Sethian (1985a, c), the Osher-Sethian (1988), level set formulation the classical shock theory of Lax (1971; 1973), as well as curve evolution theory for a curve evolving as a function of the curvature and the relation to geometric smoothing of Gage-Hamilton-Grayson (1986; 1989). The result is a characterization of the computational elements of shape: deformations, parts, bends, and seeds, which show where to place the components of a shape. The theory unifies many of the diverse aspects of shapes, and leads to a space of shapes (the reaction/diffusion space), which places shapes within a neighborhood of “similar” ones. Such similarity relationships underlie descriptions suitable for recognition.

The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene.

Abstract: In mice, natural resistance or susceptibility to infection with intracellular parasites is determined by a locus or group of loci on chromosome 1, designated Bcg, Lsh, and Ity, which controls early microbial replication in reticuloendothelial organs. We have identified by positional cloning a candidate gene for Bcg, Nramp1, which codes for a novel macrophage-specific membrane transport protein. We have created a mouse mutant bearing a null allele at Nramp1, and we have analyzed the effect of such a mutation on natural resistance to infection. Targeted disruption of Nramp1 has pleiotropic effects on natural resistance to infection with intracellular parasites, as it eliminated resistance to Mycobacterium bovis, Leishmania donovani, and lethal Salmonella typhimurium infection, establishing that Nramp1, Bcg, Lsh, and Ity are the same locus. Comparing the profiles of parasite replication in control and Nramp1-/- mice indicated that the Nramp1Asp169 allele of BcgS inbred strains is a null allele, pointing to a critical role of this residue in the mechanism of action of the protein. Despite their inability to control parasite growth in the early nonimmune phase of the infection, Nramp1-/- mutants can overcome the infection in the late immune phase, suggesting that Nramp1 plays a key role only in the early part of the macrophage-parasite interaction and may function by a cytocidal or cytostatic mechanism distinct from those expressed by activated macrophages.

Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats

Abstract: Prolonged treatment with stress levels of corticosterone has been reported to produce changes in the hippocampus. In the experiments reported here, we examined for functional and morphological consequences of this treatment. First, young adult or mid-aged male Long-Evans rats were treated for either 1 or 3 months with corticosterone, at a dose sufficient to mimic the elevated hormone levels observed following exposure to mild stress. Two weeks following the termination of treatment, the animals were tested in the Morris water maze to assess spatial learning. No behavioral deficits were observed after 1 month of treatment. A 3 month treatment period also had no effect in young rats, but produced a learning impairment in the mid-aged rats. We then examined whether the effect of elevated corticosterone in mid-aged animals could be produced by a physiological stressor. Mid-aged rats were maintained for 6 months under conditions of low or high social stress. Six months of exposure to high social stress produced significant spatial learning impairments in the Morris water maze. These effects were absent in high social stress animals that had been previously adrenalectomized (with low-level corticosterone replacement), suggesting that elevated glucocorticoid levels mediate the effects of stress on spatial memory in older animals. In a final experiment, mid-aged rats were treated with corticosterone at levels that mimicked those naturally occurring at the diurnal peak (medium-B: 12–17 micrograms/dl) or in response to stress (high-B: 25–32 micrograms/dl). Only rats exposed to high levels of corticosterone demonstrated impaired performance in the Morris water maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects

Abstract: Reactive oxygen species (ROS) have beneficial or detrimental effects on sperm functions depending on the nature and the concentration of the ROS involved, as well as the moment and the location of exposure. Excessive generation of ROS in semen, mainly by neutrophils but also by abnormal spermatozoa, could be a cause for infertility. Hydrogen peroxide is the primary toxic ROS for human spermatozoa. Low concentrations of this ROS do not affect sperm viability but cause sperm immobilization mostly via depletion of intracellular ATP and the subsequent decrease in the phosphorylation of axonemal proteins. High concentrations of hydrogen peroxide induce lipid peroxidation and result in cell death. On the other hand, the superoxide anion appears to play a major role in the development of hyperactivation and capacitation. The observations that: (i) exogenously generated superoxide anions induce hyperactivation and capacitation; (ii) capacitating spermatozoa themselves produce elevated concentrations of superoxide anion over prolonged periods of time; and (iii) removal of this ROS by superoxide dismutase prevents sperm hyperactivation and capacitation induced by various biological fluids, stress the importance of the superoxide anion in these processes.

Opening up Decision Making: The View from the Black Stool

Abstract: Set on its current course thirty years ago by Herbert Simon's notions of bounded rationality and sequential stages, the research literature of organizational decision making is claimed in this paper to have suffered from three major limitations labeled reification, dehumanization, and isolation. In particular, it has been stuck along a continuum between the cerebral rationality of the stage theories at one end and the apparent irrationality of the theory of organized anarchies at the other. This paper seeks to open up decision making in three respects. First, the concept of “decision” is opened up to the ambiguities that surround the relationship between commitment and action. Second, the decision maker is opened up to history and experience, to affect and inspiration, and especially to the critical role of insight in transcending the bounds of cerebral rationality. Third, the process of decision making is opened up to a host of dynamic linkages, so that isolated traces of single decisions come to be seen as interwoven networks of issues. The paper concludes with a plea to open up research itself to the development of richer theory on these important processes.

Victimization of lesbian, gay, and bisexual youth in community settings

Abstract: One hundred ninety-four lesbian, gay, and bisexual youth between the ages of 15 and 21 were surveyed about victimization due to their sexual orientation. Three areas were assessed: (1) the prevalence of different kinds of victimization, ranging from verbal abuse to armed assault; (2) the specific social contexts in which anti-lesbian/gay victimization occurred, including family, school, work, and the broader community; and (3) correlates of anti– lesbian/gay victimization, including age-related sexual orientation milestones, concealability of sexual orientation, sex, race/ethnicity, and safety fears. Most respondents had experienced some form of victimization, with no social environment being free from risk of harm. Particularly vulnerable for abuse were youth who self-labeled or self-disclosed at an earlier age and those whose sexual orientation was less concealed or concealable.

Registering multiview range data to create 3D computer objects

Abstract: Concerns the problem of range image registration for the purpose of building surface models of 3D objects. The registration task involves finding the translation and rotation parameters which properly align overlapping views of the object so as to reconstruct from these partial surfaces, an integrated surface representation of the object. The registration task is expressed as an optimization problem. We define a function which measures the quality of the alignment between the partial surfaces contained in two range images as produced by a set of motion parameters. This function computes a sum of Euclidean distances from control points on one surfaces to corresponding points on the other. The strength of this approach is in the method used to determine point correspondences. It reverses the rangefinder calibration process, resulting in equations which can be used to directly compute the location of a point in a range image corresponding to an arbitrary point in 3D space. A stochastic optimization technique, very fast simulated reannealing (VFSR), is used to minimize the cost function. Dual-view registration experiments yielded excellent results in very reasonable time. A multiview registration experiment took a long time. A complete surface model was then constructed from the integration of multiple partial views. The effectiveness with which registration of range images can be accomplished makes this method attractive for many practical applications where surface models of 3D objects must be constructed. >

Language differentiation in early bilingual development

Abstract: It has been claimed that children simultaneously acquiring two languages go through an initial stage when they are unable to differentiate between their two languages. Such claims have been based on the observation that at times virtually all bilingual children mix elements (e.g. lexical, morphological) from their two languages in the same utterance. That most, if not all, children acquiring two languages simultaneously mix linguistic elements in this way is widely documented. Although such code-mixing is not well understood or explained, there are a number of explanations unrelated to lack of language differentiation that may explain it. Moreover, while language differentiation is widely attested among bilingual children once functional categories emerge, usually during the third year, there is still some question as to how early in development differentiation is present. In this study, we examined language differentiation in five bilingual children prior to the emergence of functional categories (they ranged in age from 1;10 to 2;2 and in MLU from 1.23 to 2.08). They were observed with each parent separately and both together, on separate occasions. Our results indicate that while these children did code mix, they were clearly able to differentiate between their two languages. We also examine the possibility that the children's mixing is due to (a) their language dominance, and (b) their parents' rate of mixing. We could find no evidence that their mixing was due to parental input, but there was some evidence that language dominance played a role.

Fermat’s Last Theorem

Abstract: The authors would like to give special thanks to N. Boston, K. Buzzard, and B. Conrad for providing so much valuable feedback on earlier versions of this paper. They are also grateful to A. Agboola, M. Bertolini, B. Edixhoven, J. Fearnley, R. Gross, L. Guo, F. Jarvis, H. Kisilevsky, E. Liverance, J. Manoharmayum, K. Ribet, D. Rohrlich, M. Rosen, R. Schoof, J.-P. Serre, C. Skinner, D. Thakur, J. Tilouine, J. Tunnell, A. Van der Poorten, and L. Washington for their helpful comments. Darmon thanks the members of CICMA and of the Quebec-Vermont Number Theory Seminar for many stimulating conversations on the topics of this paper, particularly in the Spring of 1995. For the same reason Diamond is grateful to the participants in an informal seminar at Columbia University in 1993-94, and Taylor thanks those attending the Oxford Number Theory Seminar in the Fall of 1995.