Showing papers by "University of Toronto published in 2000"

The Sloan Digital Sky Survey: Technical summary

Abstract: The Sloan Digital Sky Survey (SDSS) will provide the data to support detailed investigations of the distribution of luminous and nonluminous matter in the universe: a photometrically and astrometrically calibrated digital imaging survey of π sr above about Galactic latitude 30° in five broad optical bands to a depth of g' ~ 23 mag, and a spectroscopic survey of the approximately 106 brightest galaxies and 105 brightest quasars found in the photometric object catalog produced by the imaging survey. This paper summarizes the observational parameters and data products of the SDSS and serves as an introduction to extensive technical on-line documentation.

Neuronal plasticity: increasing the gain in pain.

Abstract: We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.

Individual differences in reasoning: Implications for the rationality debate?

Abstract: Much research in the last two decades has demon- strated that human responses deviate from the performance deemed normative according to various models of decision mak- ing and rational judgment (e.g., the basic axioms of utility theory). This gap between the normative and the descriptive can be inter- preted as indicating systematic irrationalities in human cognition. However, four alternative interpretations preserve the assumption that human behavior and cognition is largely rational. These posit that the gap is due to (1) performance errors, (2) computational limitations, (3) the wrong norm being applied by the experi- menter, and (4) a different construal of the task by the subject. In the debates about the viability of these alternative explanations, attention has been focused too narrowly on the modal response. In a series of experiments involving most of the classic tasks in the heuristics and biases literature, we have examined the implica- tions of individual differences in performance for each of the four explanations of the normative/descriptive gap. Performance er- rors are a minor factor in the gap; computational limitations un- derlie non-normative responding on several tasks, particularly those that involve some type of cognitive decontextualization. Un- expected patterns of covariance can suggest when the wrong norm is being applied to a task or when an alternative construal of the task should be considered appropriate.

Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer

Abstract: Background The combination of fluorouracil and leucovorin has until recently been standard therapy for metastatic colorectal cancer. Irinotecan prolongs survival in patients with colorectal cancer that is refractory to treatment with fluorouracil and leucovorin. In a multicenter trial, we compared a combination of irinotecan, fluorouracil, and leucovorin with bolus doses of fluorouracil and leucovorin as first-line therapy for metastatic colorectal cancer. A third group of patients received irinotecan alone. Methods Patients were randomly assigned to receive irinotecan (125 mg per square meter of body-surface area intravenously), fluorouracil (500 mg per square meter as an intravenous bolus), and leucovorin (20 mg per square meter as an intravenous bolus) weekly for four weeks every six weeks; fluorouracil (425 mg per square meter as an intravenous bolus) and leucovorin (20 mg per square meter as an intravenous bolus) daily for five consecutive days every four weeks; or irinotecan alone (125 mg per square...

Don't go it alone: alliance network composition and startups' performance in Canadian biotechnology

Abstract: We combine theory and research on alliance networks and on new firms to investigate the impact of variation in startups’ alliance network composition on their early performance. We hypothesize that startups can enhance their early performance by 1) establishing alliances, 2) configuring them into an efficient network that provides access to diverse information and capabilities with minimum costs of redundancy, conflict, and complexity, and 3) judiciously allying with potential rivals that provide more opportunity for learning and less risk of intra-alliance rivalry. An analysis of Canadian biotech startups’ performance provides broad support for our hypotheses, especially as they relate to innovative performance. Overall, our findings show how variation in the alliance networks startups configure at the time of their founding produces significant differences in their early performance, contributing directly to an explanation of how and why firm age and size affect firm performance. We discuss some clear, but challenging, implications for managers of startups. Copyright © 2000 John Wiley & Sons, Ltd.

A flat Universe from high-resolution maps of the cosmic microwave background radiation

Abstract: The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73 K cosmic microwave background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the Universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole l_(peak) = (197 ± 6), with an amplitude ΔT_(200) = (69 ± 8) µK. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary models.

Markov Chain Sampling Methods for Dirichlet Process Mixture Models

Abstract: This article reviews Markov chain methods for sampling from the posterior distribution of a Dirichlet process mixture model and presents two new classes of methods. One new approach is to make Metropolis—Hastings updates of the indicators specifying which mixture component is associated with each observation, perhaps supplemented with a partial form of Gibbs sampling. The other new approach extends Gibbs sampling for these indicators by using a set of auxiliary parameters. These methods are simple to implement and are more efficient than previous ways of handling general Dirichlet process mixture models with non-conjugate priors.

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non–Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy

Abstract: PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patient...

Requirements engineering: a roadmap

Abstract: This paper presents an overview of the field of software systems requirements engineering (RE). It describes the main areas of RE practice, and highlights some key open research issues for the future.

Redundant governance structures: an analysis of structural and relational embeddedness in the steel and semiconductor industries

Abstract: Network researchers have argued that both relational embeddedness—characteristics of relationships—and structural embeddedness—characteristics of the relational structure—influence firm behavior and performance. Using strategic alliance networks in the semiconductor and steel industries, we build on past embeddedness research by examining the interaction of these factors. We argue that the roles relational and structural embeddedness play in firm performance can only be understood with reference to the other. Moreover, we argue that the influence of these factors on firm performance is contingent on industry context. More specifically, our empirical analysis suggests that strong ties in a highly interconnected strategic alliance network negatively impact firm performance. This network configuration is especially suboptimal for firms in the semiconductor industry. Furthermore, strong and weak ties are positively related to firm performance in the steel and semiconductor industries, respectively. Copyright © 2000 John Wiley & Sons, Ltd.

A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis

Abstract: Background Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown. Methods We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing. Results As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, ...

Motivating the Academically Unmotivated: A Critical Issue for the 21st Century:

Abstract: Interests and goals have been identified as two important motivational variables that impact individuals' academic performances, yet little is known about how best to utilize these variables to enhance childrens' learning. We first review recent developments in the two areas and then examine the connection between interests and goals. We argue that the polarization of situational and individual interest, extrinsic and intrinsic motivation, and performance and mastery goals must be reconsidered. In addition, although we acknowledge the positive effects of individual interest, intrinsic motivation, and the adoption of mastery goals, we urge educators and researchers to recognize the potential additional benefits of externally triggered situational interest, extrinsic motivation, and performance goals. Only by dealing with the multidimensional nature of motivational forces will we be able to help our academically unmotivated children.

The Plasma Boundary of Magnetic Fusion Devices

Abstract: The Plasma Boundary of Magnetic Fusion Devices introduces the physics of the plasma boundary region, including plasma-surface interactions, with an emphasis on those occurring in magnetically confined fusion plasmas. The book covers plasma-surface interaction, Debye sheaths, sputtering, scrape-off layers, plasma impurities, recycling and control, 1D and 2D fluid and kinetic modeling of particle transport, plasma properties at the edge, diverter and limiter physics, and control of the plasma boundary.Divided into three parts, the book begins with Part 1, an introduction to the plasma boundary. The derivations are heuristic and worked problems help crystallize physical intuition, which is emphasized throughout. Part 2 provides an introduction to methods of modeling the plasma edge region and for interpreting computer code results. Part 3 presents a collection of essays on currently active research hot topics.With an extensive bibliography and index, this book is an invaluable first port-of-call for researchers interested in plasma-surface interactions.

An Anatomy of Adaptation to Climate Change and Variability

Abstract: Adaptation to climate variability and change is important both for impact assessment (to estimate adaptations which are likely to occur) and for policy development (to advise on or prescribe adaptations). This paper proposes an "anatomy of adaptation" to systematically specify and differentiate adaptations, based upon three questions: (i) adapt to what? (ii) who or what adapts? and (iii) how does adaptation occur? Climatic stimuli include changes in long-term mean conditions and variability about means, both current and future, and including extremes. Adaptation depends fundamentally on the characteristics of the system of interest, including its sensitivities and vulnerabilities. The nature of adaptation processes and forms can be distinguished by numerous attributes including timing, purposefulness, and effect. The paper notes the contribution of conceptual and numerical models and empirical studies to the understanding of adaptation, and outlines approaches to the normative evaluation of adaptation measures and strategies.

Large-scale synthesis of a silicon photonic crystal with a complete three-dimensional bandgap near 1.5 micrometres

Abstract: Photonic technology, using light instead of electrons as the information carrier, is increasingly replacing electronics in communication and information management systems. Microscopic light manipulation, for this purpose, is achievable through photonic bandgap materials1,2, a special class of photonic crystals in which three-dimensional, periodic dielectric constant variations controllably prohibit electromagnetic propagation throughout a specified frequency band. This can result in the localization of photons3,4,5,6, thus providing a mechanism for controlling and inhibiting spontaneous light emission that can be exploited for photonic device fabrication. In fact, carefully engineered line defects could act as waveguides connecting photonic devices in all-optical microchips7, and infiltration of the photonic material with suitable liquid crystals might produce photonic bandgap structures (and hence light-flow patterns) fully tunable by an externally applied voltage8,9,10. However, the realization of this technology requires a strategy for the efficient synthesis of high-quality, large-scale photonic crystals with photonic bandgaps at micrometre and sub-micrometre wavelengths, and with rationally designed line and point defects for optical circuitry. Here we describe single crystals of silicon inverse opal with a complete three-dimensional photonic bandgap centred on 1.46 µm, produced by growing silicon inside the voids of an opal template of close-packed silica spheres that are connected by small ‘necks’ formed during sintering, followed by removal of the silica template. The synthesis method is simple and inexpensive, yielding photonic crystals of pure silicon that are easily integrated with existing silicon-based microelectronics.

Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

Abstract: Much evidence indicates that abnormal processing and extracellular deposition of amyloid-β peptide (Aβ), a proteolytic derivative of the β-amyloid precursor protein (βAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with Aβ causes a marked reduction in burden of the brain amyloid2,3. Evidence that Aβ immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal Aβ processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the ‘amyloid cascade’. Here we show that Aβ immunization reduces both deposition of cerebral fibrillar Aβ and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of Aβ in the brain. This implies that either a ∼50% reduction in dense-cored Aβ plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic Aβ species.

Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

Abstract: Hereditary Hemorrhagic Telangiectasia (HHT) is easily recognized in individuals displaying the classical triad of epistaxis, telangiectasia, and a suitable family history, but the disease is more difficult to diagnosis in many patients. Serious consequences may result if visceral arteriovenous malformations, particularly in the pulmonary circulation, are unrecognized and left untreated. In spite of the identification of two of the disease-causing genes (endoglin and ALK-1), only a clinical diagnosis of HHT can be provided for the majority of individuals. On behalf of the Scientific Advisory Board of the HHT Foundation International, Inc., we present consensus clinical diagnostic criteria. The four criteria (epistaxes, telangiectasia, visceral lesions and an appropriate family history) are carefully delineated. The HHT diagnosis is definite if three criteria are present. A diagnosis of HHT cannot be established in patients with only two criteria, but should be recorded as possible or suspected to maintain a high index of clinical suspicion. If fewer than two criteria are present, HHT is unlikely, although children of affected individuals should be considered at risk in view of age-related penetration in this disorder. These criteria may be refined as molecular diagnostic tests become available in the next few years.

Clock-drawing: is it the ideal cognitive screening test?

Abstract: Objective. The clock-drawing test has achieved widespread clinical use in recent years as a cognitive screening instrument and a significant amount of literature relates to its psychometric properties and clinical utility. This review aims to synthesize the available evidence and assess the value of this screening test according to well-defined criteria. Design. A Medline and Psycho-info literature search of all languages was done from 1983 to 1998 including manual cross-referencing of bibliographies. A brief summary of all original scoring systems is provided as well as a review of replication studies. Psychometric data including correlations with other cognitive tests were recorded. Qualitative aspects of the test are also described. Results. Among published studies, the mean sensitivity (85%) and specificity (85%) of the clock-drawing test are impressive. Correlations with the Mini-Mental State Examination and other cognitive tests was high, generally greater than r = 0.5. High levels of inter-rater and test–re-test reliability and positive predictive value are recorded and despite significant variability in the scoring systems, all report similar psychometric properties. The clock test also shows a sensitivity to cognitive change with good predictive validity. Conclusions. The clock-drawing test meets defined criteria for a cognitive screening instrument. It taps into a wide range of cognitive abilities including executive functions, is quick and easy to administer and score with excellent acceptability by subjects. Together with informant reports, the clock-drawing test is complementary to the widely used and validated Mini-Mental State Examination and should provide a significant advance in the early detection of dementia and in monitoring cognitive change. A simple scoring system with emphasis on the qualitative aspects of clock-drawing should maximize its utility. Copyright © 2000 John Wiley & Sons, Ltd.

MAXIMA-1: A measurement of the cosmic microwave background anisotropy on angular scales of 10′-5°

Abstract: We present a map and an angular power spectrum of the anisotropy of the cosmic microwave background (CMB) from the first flight of MAXIMA. MAXIMA is a balloon-borne experiment with an array of 16 bolometric photometers operated at 100 mK. MAXIMA observed a 124 deg region of the sky with 10' resolution at frequencies of 150, 240 and 410 GHz. The data were calibrated using in-flight measurements of the CMB dipole anisotropy. A map of the CMB anisotropy was produced from three 150 and one 240 GHz photometer without need for foreground subtractions. Analysis of this CMB map yields a power spectrum for the CMB anisotropy over the range 36 {le} {ell} {le} 785. The spectrum shows a peak with an amplitude of 78 {+-} 6 {mu}K at {ell} {approx_equal} 220 and an amplitude varying between {approx} 40 {mu}K and {approx} 50 {mu}K for 400 {approx}< {ell} {approx}< 785.

Nursery Cities: Urban Diversity, Process Innovation and the Life-Cycle of Products

Abstract: A simple model of process innovation is proposed, where firms learn about their ideal production process by making prototypes. We build around this a dynamic general equilibrium model, and derive conditions under which diversified and specialised cities coexist. New products are developed in diversified cities, trying processes borrowed from different activities. On finding their ideal process, firms switch to mass-production and relocate to specialised cities with lower costs. When in equilibrium, this configuration welfare-dominates those with only diversified or only specialised cities. We find strong evidence of this relocation pattern in establishment relocations across French employment areas 1993u1996.

Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration

Abstract: Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3Kgamma links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.

Retinal Stem Cells in the Adult Mammalian Eye

Abstract: The mature mammalian retina is thought to lack regenerative capacity. Here, we report the identification of a stem cell in the adult mouse eye, which represents a possible substrate for retinal regeneration. Single pigmented ciliary margin cells clonally proliferate in vitro to form sphere colonies of cells that can differentiate into retinal-specific cell types, including rod photoreceptors, bipolar neurons, and Muller glia. Adult retinal stem cells are localized to the pigmented ciliary margin and not to the central and peripheral retinal pigmented epithelium, indicating that these cells may be homologous to those found in the eye germinal zone of other nonmammalian vertebrates.

Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation

Abstract: The hexosamine pathway has been implicated in the pathogenesis of diabetic complications. We determined first that hyperglycemia induced a decrease in glyceraldehyde-3-phosphate dehydrogenase activity in bovine aortic endothelial cells via increased production of mitochondrial superoxide and a concomitant 2.4-fold increase in hexosamine pathway activity. Both decreased glyceraldehyde-3-phosphate dehydrogenase activity and increased hexosamine pathway activity were prevented completely by an inhibitor of electron transport complex II (thenoyltrifluoroacetone), an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), a superoxide dismutase mimetic [manganese (III) tetrakis(4-benzoic acid) porphyrin], overexpression of either uncoupling protein 1 or manganese superoxide dismutase, and azaserine, an inhibitor of the rate-limiting enzyme in the hexosamine pathway (glutamine:fructose-6-phosphate amidotransferase). Immunoprecipitation of Sp1 followed by Western blotting with antibodies to O-linked GlcNAc, phosphoserine, and phosphothreonine showed that hyperglycemia increased GlcNAc by 1.7-fold, decreased phosphoserine by 80%, and decreased phosphothreonine by 70%. The same inhibitors prevented all these changes. Hyperglycemia increased expression from a transforming growth factor-β1 promoter luciferase reporter by 2-fold and increased expression from a (−740 to +44) plasminogen activator inhibitor-1 promoter luciferase reporter gene by nearly 3-fold. Inhibition of mitochondrial superoxide production or the glucosamine pathway prevented all these changes. Hyperglycemia increased expression from an 85-bp truncated plasminogen activator inhibitor-1 (PAI-1) promoter luciferase reporter containing two Sp1 sites in a similar fashion (3.8-fold). In contrast, hyperglycemia had no effect when the two Sp1 sites were mutated. Thus, hyperglycemia-induced mitochondrial superoxide overproduction increases hexosamine synthesis and O-glycosylation of Sp1, which activates expression of genes that contribute to the pathogenesis of diabetic complications.

Hypersensitive response-related death.

Abstract: The hypersensitive response (HR) of plants resistant to microbial pathogens involves a complex form of programmed cell death (PCD) that differs from developmental PCD in its consistent association with the induction of local and systemic defence responses. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen avirulence gene products and those of plant resistance genes and it can be the result of multiple signalling pathways. Ion fluxes and the generation of reactive oxygen species commonly precede cell death, but a direct involvement of the latter seems to vary with the plant-pathogen combination. Protein synthesis, an intact actin cytoskeleton and salicylic acid also seem necessary for cell death induction. Cytological studies suggest that the actual mode and sequence of dismantling the cell contents varies among plant-parasite systems although there may be a universal involvement of cysteine proteases. It seems likely that cell death within the HR acts more as a signal to the rest of the plant rather than as a direct defence mechanism.