Showing papers by "McGill University published in 1994"

Statistical parametric maps in functional imaging: A general linear approach

Abstract: + Abstract: Statistical parametric maps are spatially extended statistical processes that are used to test hypotheses about regionally specific effects in neuroimaging data. The most established sorts of statistical parametric maps (e.g., Friston et al. (1991): J Cereb Blood Flow Metab 11:690-699; Worsley et al. 119921: J Cereb Blood Flow Metab 12:YOO-918) are based on linear models, for example ANCOVA, correlation coefficients and t tests. In the sense that these examples are all special cases of the general linear model it should be possible to implement them (and many others) within a unified framework. We present here a general approach that accommodates most forms of experimental layout and ensuing analysis (designed experiments with fixed effects for factors, covariates and interaction of factors). This approach brings together two well established bodies of theory (the general linear model and the theory of Gaussian fields) to provide a complete and simple framework for the analysis of imaging data. The importance of this framework is twofold: (i) Conceptual and mathematical simplicity, in that the same small number of operational equations is used irrespective of the complexity of the experiment or nature of the statistical model and (ii) the generality of the framework provides for great latitude in experimental design and analysis.

Customer Loyalty: Toward an Integrated Conceptual Framework:

Abstract: Customer loyalty is viewed as the strength of the relationship between an individual’s relative attitude and repeat patronage. The relationship is seen as mediated by social norms and situational factors. Cognitive, affective, and conative antecedents of relative attitude are identified as contributing to loyalty, along with motivational, perceptual, and behavioral consequences. Implications for research and for the management of loyalty are derived.

A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1

Abstract: A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.

Introduction to surface chemistry and catalysis

Abstract: Preface. Introduction. 1 Surfaces: An Introduction. 2 The Structure of Surfaces. 3 Thermodynamics of Surfaces. 4 Dynamics at Surfaces. 5 Electrical Properties of Surfaces. 6 Surface Chemical Bond. 7 Mechanical Properties of Surfaces. 8 Polymer Surfaces and Biointerfaces. 9 Catalysis by Surfaces. Index.

Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13

Abstract: A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.

A comprehensive classification of thoracic and lumbar injuries

Abstract: In view of the current level of knowledge and the numerous treatment possibilities, none of the existing classification systems of thoracic and lumbar injuries is completely satisfactory As a result of more than a decade of consideration of the subject matter and a review of 1445 consecutive thoracolumbar injuries, a comprehensive classification of thoracic and lumbar injuries is proposed The classification is primarily based on pathomorphological criteria Categories are established according to the main mechanism of injury, pathomorphological uniformity, and in consideration of prognostic aspects regarding healing potential The classification reflects a progressive scale of morphological damage by which the degree of instability is determined The severity of the injury in terms of instability is expressed by its ranking within the classification system A simple grid, the 3-3-3 scheme of the AO fracture classification, was used in grouping the injuries This grid consists of three types: A, B, and C Every type has three groups, each of which contains three subgroups with specifications The types have a fundamental injury pattern which is determined by the three most important mechanisms acting on the spine: compression, distraction, and axial torque Type A (vertebral body compression) focuses on injury patterns of the vertebral body Type B injuries (anterior and posterior element injuries with distraction) are characterized by transverse disruption either anteriorly or posteriorly Type C lesions (anterior and posterior element injuries with rotation) describe injury patterns resulting from axial torque The latter are most often superimposed on either type A or type B lesions Morphological criteria are predominantly used for further subdivision of the injuries Severity progresses from type A through type C as well as within the types, groups, and further subdivisions The 1445 cases were analyzed with regard to the level of the main injury, the frequency of types and groups, and the incidence of neurological deficit Most injuries occurred around the thoracolumbar junction The upper and lower end of the thoracolumbar spine and the T 10 level were most infrequently injured Type A fractures were found in 661 %, type B in 145%, and type C in 194% of the cases Stable type Al fractures accounted for 347% of the total Some injury patterns are typical for certain sections of the thoracolumbar spine and others for age groups The neurological deficit, ranging from complete paraplegia to a single root lesion, was evaluated in 1212 cases The overall incidence was 22% and increased significantly from type to type: neurological deficit was present in 14% of type A, 32% of type B, and 55% of type C lesions Only 2% of the Al and 4% of the A2 fractures showed any neurological deficit The classification is comprehensive as almost any injury can be itemized according to easily recognizable and consistent radiographic and clinical findings Every injury can be defined alphanumerically or by a descriptive name The classification can, however, also be used in an abbreviated form without impairment of the information most important for clinical practice Identification of the fundamental nature of an injury is facilitated by a simple algorithm Recognizing the nature of the injury, its degree of instability, and prognostic aspects are decisive for the choice of the most appropriate treatment Experience has shown that the new classification is especially useful in this respect

Explaining the Role of User Participation in Information System Use

Abstract: Even though user participation in information system development has long been considered to be a critical factor in achieving system success, research has failed to clearly demonstrate its benefits. This paper proposes user involvement as an intervening variable between user participation and system use. Embedding the constructs of participation and involvement into the theoretical framework of Fishbein and Ajzen, a model is developed and tested in a field study of information system projects. Several key findings emerge from the study. User participation and user involvement represent two distinct constructs, with participation leading to involvement, and involvement mediating the relationship between participation and system use. The critical dimension of user participation is overall responsibility. The role of user participation and involvement is different, depending upon whether system use is mandatory or voluntary.

Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function

Abstract: The cloning is described of two related human complementary DNAs encoding polypeptides that interact specifically with the translation initiation factor eIF-4E, which binds to the messenger RNA 5'-cap structure. Interaction of these proteins with eIF-4E inhibits translation but treatment of cells with insulin causes one of them to become hyperphosphorylated and dissociate from eIF-4E, thereby relieving the translational inhibition. The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth.

Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.

Abstract: Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.

Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification

Abstract: Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90-bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to porcine MTHFR and to bacterial metF genes. The human gene has been localized to chromosome 1p36.3. Two mutations were identified in MTHFR-deficient patients: a missense mutation (Arg to Gln), in a residue conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter).

Modelling food chain structure and contaminant bioaccumulation using stable nitrogen isotopes

Abstract: THE nitrogen pools of animals are enriched in 15N relative to their food1, with the top predators having the highest concentrations of this stable isotope2. The use of δ15N to indicate trophic position depends on the degree to which it reflects variation in the underly-ing food-web structure, rather than variable fractionation along the food chain. Here we compare adult lake trout, a top pelagic predator, from a series of lakes, and find that δ15N values vary from 7.5 to 17.5%o, a surprisingly wide range for one species. The length of the food chain can explain this variation, supporting the idea that δ15N is a food-web descriptor. Food-chain length was measured by the presence or absence of two intermediate trophic levels, pelagic forage fish and the macrozooplankter, Mysis relicta, each of which when present contributes about three δ15N units to the trout signature. We find that δ15N can be used as a continuous, integrative measure of trophic position, which is supported by its correlation to mercury levels in lake trout.

On black hole entropy

Abstract: Two techniques for computing black hole entropy in generally covariant gravity theories including arbitrary higher derivative interactions are studied. The techniques are Wald's Noether charge approach introduced recently, and a field redefinition method developed in this paper. Wald's results are extended by establishing that his local geometric expression for the black hole entropy gives the same result when evaluated on an arbitrary cross section of a Killing horizon (rather than just the bifurcation surface). Further, we show that his expression for the entropy is not affected by ambiguities which arise in the Noether construction. Using the Noether charge expression, the entropy is evaluated explicitly for black holes in a wide class of generally covariant theories. For a Lagrangian of the functional form L\ifmmode \tilde{}\else \~{}\fi{}=L\ifmmode \tilde{}\else \~{}\fi{}(${\mathrm{\ensuremath{\psi}}}_{\mathit{m}}$, ${\mathrm{\ensuremath{ abla}}}_{\mathit{a}}$${\mathrm{\ensuremath{\psi}}}_{\mathit{m}}$,${\mathit{g}}_{\mathit{a}\mathit{b}}$,${\mathit{R}}_{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$, ${\mathrm{\ensuremath{ abla}}}_{\mathit{e}}$${\mathit{R}}_{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$), it is found that the entropy is given by S=-2\ensuremath{\pi}\ensuremath{\oint}(${\mathit{Y}}^{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$-${\mathrm{\ensuremath{ abla}}}_{\mathit{e}}$${\mathit{Z}}^{\mathit{e}:\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$) \ensuremath{\epsilon}${\mathrm{^}}_{\mathit{a}\mathit{b}}$\ensuremath{\epsilon}${\mathrm{^}}_{\mathit{c}\mathit{d}}$\ensuremath{\epsilon}\ifmmode\bar\else\textasciimacron\fi{}, where the integral is over an arbitrary cross section of the Killing horizon, \ensuremath{\epsilon}${\mathrm{^}}_{\mathit{a}\mathit{b}}$ is the binormal to the cross section, ${\mathit{Y}}^{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$=\ensuremath{\partial}L\ifmmode \tilde{}\else \~{}\fi{}/\ensuremath{\partial}${\mathit{R}}_{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$, and ${\mathit{Z}}^{\mathit{e}:\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$=\ensuremath{\partial}L\ifmmode \tilde{}\else \~{}\fi{}/\ensuremath{\partial}${\mathrm{\ensuremath{ abla}}}_{\mathit{e}}$${\mathit{R}}_{\mathit{a}\mathit{b}\mathit{c}\mathit{d}}$.Further, it is shown that the Killing horizon and surface gravity of a stationary black hole metric are invariant under field redefinitions of the metric of the form g${\mathrm{\ifmmode\bar\else\textasciimacron\fi{}}}_{\mathit{a}\mathit{b}}$\ensuremath{\equiv}${\mathit{g}}_{\mathit{a}\mathit{b}}$+${\mathrm{\ensuremath{\Delta}}}_{\mathit{a}\mathit{b}}$, where ${\mathrm{\ensuremath{\Delta}}}_{\mathit{a}\mathit{b}}$ is a stationary tensor field that vanishes at infinity and is regular on the horizon (including the bifurcation surface). Using this result, a technique is developed for evaluating the black hole entropy in a given theory in terms of that of another theory related by field redefinitions. Remarkably, it is established that certain perturbative, first order, results obtained with this method are in fact exact. A particular result established in this fashion is that a scalar matter term of the form ${\mathrm{\ensuremath{ abla}}}^{2\mathit{p}}$\ensuremath{\varphi}${\mathrm{\ensuremath{ abla}}}^{2\mathit{q}}$\ensuremath{\varphi} in the Lagrangian makes no contribution to the black hole entropy. The possible significance of these results for the problem of finding the statistical origin of black hole entropy is discussed.

Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis.

Abstract: The mechanisms involved in the initiation and maintenance of skin inflammation in atopic dermatitis (AD) are poorly understood. Recent data suggest that the pattern of cytokines expressed locally plays a critical role in modulating the nature of tissue inflammation. In this study, we used in situ hybridization to investigate the expression of interleukin 4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) messenger RNA (mRNA) in skin biopsies from acute and chronic skin lesions of patients with AD. As compared with normal control skin or uninvolved skin of patients with AD, acute and chronic skin lesions had significantly greater numbers of cells that were positive for mRNA, IL-4 (P < 0.01), and IL-5 (P < 0.01), but not for IFN-gamma mRNA expressing cells. However, as compared with acute AD skin lesions, chronic AD skin lesions had significantly fewer IL-4 mRNA-expressing cells (P < 0.01), but significantly greater IL-5 mRNA (P < 0.01). T cells constituted the majority of IL-5-expressing cells in acute and chronic AD lesions. Chronic lesions also expressed significantly greater numbers of activated EG2+ eosinophils than acute lesions (P < 0.01). These data indicate that although acute and chronic AD lesions are associated with increased activation of IL-4 and IL-5 genes, initiation of acute skin inflammation in AD is associated with a predominance of IL-4 expression whereas maintenance of chronic inflammation is predominantly associated with increased IL-5 expression and eosinophil infiltration.

Developmental Changes in Perception of Nonnative Vowel Contrasts

Abstract: Discrimination of 2 German vowel contrasts was examined in English-learning infants of 6-8 and 10-12 months of age using a head turn procedure. The younger infants were better able than the older infants to discriminate the nonnative contrasts, but performance at 6-8 months was below levels that have been reported for nonnative consonant contrasts. A 2nd experiment using a habituation looking procedure showed that 4-month-old infants discriminated both German vowel contrasts, but the 6-month-olds could not. The findings are consistent with previous consonant work, revealing a shift from a language-general toward a language-specific pattern during the 1st year of life. However, that shift begins earlier in development for vowels than for consonants. There is a substantial body of research on developmental differences in discriminatio n of nonnative phonetic contrasts, but the research to date has focused almost exclusively on the perception of consonants. In the present study, we investigated developmental changes across infancy in discrimination of nonnative vowel contrasts. The existing cross-language research suggests that an important part of early language acquisition involves the tuning of perceptual sensitivities to map on to those required in the native language. For example, cross-language studies of consonant discrimination have revealed that young infants can discriminate nearly every phonetic contrast on which they have been tested, including those contrasts that comprise phones that are not used to distinguish meaning in their language-learning environment (for a review, see Best, in press; Werker, 1991). In an early study, Streeter (1976) showed that Kikuyu-learning infants aged 4 months could discriminate the English voiced-voiceless distinction even though it is not used phonemically in their native language. Similar findings have been reported for many other nonnative consonant contrasts (Aslin, Pisoni,

Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV.

Abstract: A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia. To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8+ T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.

Context-sensitive interprocedural points-to analysis in the presence of function pointers

Abstract: This paper reports on the design, implementation, and empirical results of a new method for dealing with the aliasing problem in C. The method is based on approximating the points-to relationships between accessible stack locations, and can be used to generate alias pairs, or used directly for other analyses and transformations.Our method provides context-sensitive interprocedural information based on analysis over invocation graphs that capture all calling contexts including recursive and mutually-recursive calling contexts. Furthermore, the method allows the smooth integration for handling general function pointers in C.We illustrate the effectiveness of the method with empirical results from an implementation in the McCAT optimizing/parallelizing C compiler.

Regulation of tumour necrosis factor-α processing by a metalloproteinase inhibitor

Abstract: Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages. TNF-alpha is synthesized as a precursor protein of M(r) 26,000 (26K) which is processed to a secreted 17K mature form by cleavage of an Ala-Val bond between residues 76-77. The enzyme(s) responsible for processing pro-TNF-alpha has yet to be identified. Here, we describe the capacity of a metalloproteinase inhibitor, GI 129471, to block TNF-alpha secretion both in vitro and in vivo. The inhibition is specific to TNF-alpha; the production of other secreted cytokines, such as the interleukins IL-1 beta, IL-2, or IL-6, is not inhibited. The mechanism of inhibition occurs at a post-translational step in TNF-alpha production. Our data suggest that TNF-alpha processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF-alpha associated pathologies.