Showing papers by "Memorial University of Newfoundland published in 1994"

Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients

Abstract: A replication error (RER) phenotype has been documented both in sporadic colorectal tumors and in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+. All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14 (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1) derived from members of HNPCC families. These data suggest the involvement of mismatch repair deficiency in the premalignant stage of tumorigenesis in HNPCC cases, and suggest that mismatch repair genes (MSH2 or others) are defective in the germline of nearly all these patients.

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.

Abstract: Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds.

Abstract: It has recently been shown that hereditary nonpolyposis colorectal cancer (HNPCC) is caused by hereditable defects in DNA mismatch repair genes However, the fraction of HNPCC due to defects in any one repair gene and the nature of these mutations are not known We analyzed 29 HNPCC kindreds for mutations in the prototype DNA mismatch repair gene hMSH2 by a combination of linkage analysis, polymerase chain reaction-based screening, and sequencing of the coding region The complete intron/exon structure of the gene was ascertained to facilitate this analysis The results suggest that at least 40% of classic HNPCC kindreds are associated with germline mutations in hMSH2 and that most of these mutations produce drastic alterations in the predicted protein product

Tabu search for the job shop scheduling problem with multi-purpose machines

Abstract: In this paper we study the following generalization of the job-shop scheduling problem. Each operation can be performed by one machine out of a set of machines given for this operation. The processing time does not depend on the machine which has been chosen for processing the operation. This problem arises in the area of flexible manufacturing. As a generalization of the jobshop problem it belongs to the hardest problems in combinatorial optimization. We show that an application of tabu search techniques to this problem yields excellent results for benchmark problems.

Close to the customer: But is it really a relationship?

Abstract: Everyone is developing relationships. Customers are being invited to have relationships with telephone companies, banks, auto dealers, airlines, and other suppliers of products and services. Relationship marketing is being touted as an effective strategy to guide companies into the next millennium. Recently there has been widespread reference to relationship marketing in the popular literature, and the concept has been embraced by many companies and organizations. There is little consensus, however, on what the concept means and even less consistency in how it is practised. What is relationship marketing? Practising marketers and articles in the trade press use the term in one way, while authors in academic journals seem often to be referring to something quite different. This paper reviews how the concept has been viewed by marketing authors and draws from social psychology to shed light on the characteristics of relationships. Some insights are drawn from a preliminary analysis of the results of focus g...

Hexanal as an indicator of meat flavor deterioration

Abstract: Pentanal and hexanal were the dominant volatile aldehydes generated from cooked pork during 3 weeks of refrigerated storage Moreover, hexanal concentrations may serve as an index of meat flavor deterioration (MFD) during the early stages of storage; its concentration increased more rapidly than any other aldehyde During the first 6 days, contribution of pentanal and hexanal to the total volatile aldehydes increased linearly by 350 and 650%, respectively, after which, their concentrations declined quite markedly Reactions of pentanal and hexanal with meat components and/or their further oxidation may be responsible for this observation Therefore, caution should be exercised when using hexanal as an indicator of lipid oxidation and MFD since a given hexanal level may correspond with two different points during storage of cooked meats

Risk factors for the development of left ventricular hypertrophy in a prospectively followed cohort of dialysis patients.

Abstract: The objective of this study was to determine the role of hypertension, age, anemia, and hyperparathyroidism in the pathogenesis of left ventricular hypertrophy (LVH) developing after the initiation of dialysis for ESRD. A cohort of dialysis patients who were being treated for ESRD and whose initial echocardiograms after the start of dialysis therapy do not show LVH were studied. Three hundred and thirty-nine patients have been monitored at three centers since 1985. Serial echocardiograms have been performed with M-mode and two-dimensional echocardiography. Data on blood pressure, height, weight, hemoglobin, number and type of antihypertensive medications, and the presence of functioning vascular access have been collected prospectively. Prospective data on serum calcium, serum phosphorus, alkaline phosphatase, and parathyroid hormone levels and skeletal x-rays have also been collected. By the use of set criteria and blinding to echocardiographic outcome, the presence and severity of hyperparathyroidism were graded by consensus. Fifty-one patients met eligibility criteria for inclusion; of these, 14 developed LVH (cases) and 37 did not (controls). Cases had significantly higher systolic blood pressure (P = 0.009) and were older (P = 0.01) than controls. Systolic blood pressure correlated significantly with final posterior left ventricular wall thickness (r = 0.39; P < 0.01). By the use of multivariate analysis, age and systolic blood pressure were significantly and independently associated with increased left ventricular mass index. The frequency of hyperparathyroidism was low and equal in both groups. There was a trend toward more severe anemia in cases that did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Equivalent times and one-dimensional elastic viscoplastic modelling of time-dependent stress-strain behaviour of clays

Abstract: This paper describes the recent concept of equivalent time and how it can be used in a revised version of an earlier elastic viscoplastic model for one-dimensional straining of clays. It clarifies ...

An analysis of bearingless AC motors

Abstract: Several types of AC bearingless motors are proposed. These bearingless motors have conventional four-pole stator windings and additional two-pole windings, whose currents produce radial forces acting on the rotor. General expressions of the machine inductances and radial forces are derived for the cylindrical rotor and salient-pole motors. No-load characteristics of laboratory squirrel-cage induction and reluctance-type synchronous bearingless motors are provided. The test motors were successfully driven by the control circuits. >

A method to increase contaminant tolerance in protein matrix‐assisted laser desorption/ionization by the fabrication of thin protein‐doped polycrystalline films

Abstract: This paper describes the fabrication and use of thin polycrystalline films in matrix-assisted laser desorption experiments. These films consist of microcrystals of protein-doped matrix (crystal dimensions ⩽ 1 μm). The films produce intense protein-ion currents and can be grown in the presence of high concentrations of involatile solvents (e.g., glycerol, 6 M urea) without any purification. They strongly adhere to the substrate, allowing easier washing of the film, compared to dried-droplet deposits. The films are also more uniform than dried-droplet deposits, with respect to ion production. It is suggested that matrix-assisted laser desorption/ionization samples are composed of nonlinear optical devices that function as polymer ion-current sources. These devices (protein-doped matrix crystals) can be designed and fabricated in many forms to serve the special functions required by the analytical scientist.

Interpreting pragmatic meaning when reading popular reports of science

Abstract: Ninety-one Grade 12 science students were asked to read five popular reports of science. The students were within 4 months of graduation, and all were taking at least one course of senior biology, chemistry, or physics. On average, the students had completed about four high school science courses. The reports were chosen from widely available published work appearing in newspapers, science magazines, and general interest magazines. The tasks given to students required them to interpret the pragmatic meaning of the reports, that is, the meaning of the reports in relation to the goals and intentions of the authors and the context set by the reports. The students interpreted statements in the reports with a bias towards truth ascription by attributing to the statements a higher degree of certainty than was expressed by the authors. Also, no more than one half of the students accurately understood the scientific status and role of statements when that understanding required contextualized interpretation on the basis of the relationships among statements in the reports. Implications for the development of scientific literacy follow from the fact that these students were top science students, yet they did not fully grasp the fundamentals of interpreting texts that are major sources of new scientific knowledge for most laypeople.

Nutrition and immunity: an overview.

Abstract: Historical accounts and recent epidemiologic studies have suggested a mutually aggravating relationship between malnutrition and infection. In protein-energy malnutrition, there is a significant impairment of several aspects of immunity, including cell-mediated immune responses, secretory immunoglobulin A antibody production, phagocyte function, complement system, antibody affinity and cytokine production. Several micronutrients play a crucial role in maintenance of optimum immune responses. On the other hand, excessive intake of nutrients also impairs immunity. Animals fed diets lacking in nucleotides have lower immune responses than controls but there is no enhancement of immunity when the diet contains large amounts of nucleotides. These observations have considerable practical importance in terms of designing feeding formulas.

Canola extract as an alternative natural antioxidant for canola oil

Abstract: The antioxidative activity of ethanolic extracts of canola meal at 100, 200, 500 and 1000 ppm on refined-bleached (RB) canola oil was examined and compared with commonly used synthetic antioxidants, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), BHA/BHT/monoglyceride citrate (MGC) andtert-butyl-hydroquinone (TBHQ). Stability of RB oil was monitored under Schaal oven test conditions at 65°C over a 17-d period. Progression of oxidation was monitored by weight gain, peroxide, conjugated diene, 2-thiobarbituric acid and total oxidation values. Canola extracts at 500 and 1000 ppm were more active than BHA, BHT and BHA/BHT/MGC and less effective than TBHQ at a level of 200 ppm.

Urban systems dynamics and cellular automata: Fractal structures between order and chaos

Abstract: Two-dimensional cellular automata with rules defined on a large neighbourhood are used to simulate the evolution of urban land-use patterns. Both the simulated urban areas and actual cities are shown to be fractal objects characterized by very similar dimensions. But the fractality (and hence realism) of the cellular cities appears only when the degree of stochasticity is within a relatively narrow band; otherwise the city is too uniform or too random. The same phenomenon appears in a conventional dynamic model of the evolution of a system of cities: the size distribution of urban centres assumes a fractal form (one observed in many real systems) only with a ‘fine tuning’ of the relevant parameters. Otherwise the system either evolves toward a uniform state or collapses to a single large centre. The tendency to observe such poised behaviour in both the cellular and the urban system models for realistic calibrations may be a manifestation of a phase-transition phenomenon observed in simpler deterministic cellular automata, and may represent a requirement for evolvability in real systems.

Investigating the genetic basis for ankylosing spondylitis. Linkage studies with the major histocompatibility complex region.

Abstract: Objective. To assess the hypothesis that B27 or a gene(s) in close proximity (e.g., within or near the major histocompatibility complex [MHC]) represents a disease-causing ankylosing spondylitis (AS) gene, and therefore contributes directly to the pathogenesis of this disorder. Methods. MHC haplotypes were determined by both serologic and molecular analyses in 15 multiple-case AS families from Toronto and Newfoundland. Segregation of MHC haplotypes with AS within these families was examined by linkage and identity-by-descent analyses. Attributable risk estimates for various genetic markers and for sex were calculated. Results. Linkage analyses established significant linkage between AS and the MHC, the maximal logarithm of odds (LOD) score being 3.48 at a recombination frequency (θ) of 0.05. In a second analysis in which the population association of the MHC gene HLA—B27 with AS was taken into account, the maximal LOD score was 7.5 at θ = 0.05. Identity-by-descent analyses showed a significant departure from random segregation among affected avuncular (P < 0.05) and cousin (P < 0.01) pairs. The presence of HLA—B40 in HLA—B27 positive individuals increased the risk for disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern of inheritance, with penetrance of approximately 20%. Conclusion. These data provide the first conclusive demonstration of linkage between the MHC region and AS, and confirm that genes within this region contribute directly to the genetic susceptibility for AS.

Timing of peak metamorphism and deformation along the Appalachian margin of Laurentia in Newfoundland: Silurian, not Ordovician

Abstract: U/Pb and Ar/Ar isotopic age data from the Corner Brook Lake region of the eastern Appalachian Humber zone in western Newfoundland indicate that regional deformation and peak amphibolite-facies metamorphism are Early Silurian. A lower limit on deformation is provided by a U/Pb zircon age of 434 +2/-3 Ma for a pegmatite that is affected by the regional foliation and is interpreted to be syntectonic. Monazite and rutile from a garnet-kyanite-staurolite schist, which records peak-metamorphic conditions and in which porphyroblasts have overgrown the regional foliation, gave U/Pb ages of 430 ±2 Ma and 437 ±6 Ma, respectively. Ar/Ar cooling ages for hornblende from amphibolites and muscovite from psammitic and pelitic schists range from 430 to 420 Ma. A Silurian age for deformation and metamorphism of the Laurentian margin is coincident with the timing of similar events along the Newfound-land Gondwana margin and suggests that the Silurian was a period of major continent-continent collision.

Morphine insensitive allodynia is produced by intrathecal strychnine in the lightly anesthetized rat

Abstract: The acute blockade of spinal glycinergic inhibition with intrathecal strychnine (i.t. STR; a glycine antagonist) in rats induces a change in somatosensory processing which is very similar to the sensory dysesthesia of clinical neural injury pain. In the present study, the effects of i.t. STR were examined in urethane-anesthetized rats. Noxious paw pinch (PP) or tail immersion (TI) in 55°C water evoked a pronounced pressor response, increased heart rate (HR) and desynchronized the electroencephalogram; a non-noxious, hair deflection (HD) elicited only minor cardiovascular responses. After i.t. STR (40 μg), an identical HD stimulus evoked markedly enhanced cardiovascular responses, resembling those evoked by noxious stimuli, and a HD-evoked motor withdrawal was observed. Consistent STR-dependent responses were only observed if a light plane of anesthesia was maintained for the duration of the experiment. The effects of i.t. STR were dose-dependent and reversible, lasting 15–30 min. Spinal morphine (50 μg) completely abolished the cardiovascular responses to PP and TI, but the HD-evoked, STR-dependent cardiovascular and motor withdrawal responses remained unchanged. In contrast, the non-selective excitatory amino acid antagonist, γ- d -glutamylglycine (DGG; 50 μg) was effective in suppressing both the STR-dependent cardiovascular and motor withdrawal responses. These data suggest that STR-dependent responses evoked by non-noxious stimuli are mediated by mechanisms distinct from those of conventional noxious stimuli and that i.t. STR may be useful for investigating the spinal pharmacology of somatosensory processing following the loss of spinal glycinergic inhibition.

Minimizing register requirements under resource-constrained rate-optimal software pipelining

Abstract: In this paper we address the following software pipelining problem: given a loop and a machine architecture with a fixed number of processor resources (e.g. function units), how can one construct a software-pipelined schedule which runs on the given architecture at the maximum possible iteration rate (ag la rate-optimal) while minimizing the number of registers?The main contributions of this paper are:•First, we demonstrate that such problem can be described by a simple mathematical formulation with precise optimization objectives under periodic linear scheduling framework. The mathematical formulation provides a clear picture which permits one to visualize the overall solution space (for rate-optimal schedules) under different sets of constraints.•Secondly, we show that a precise mathematical formulation and its solution does make a significant performance difference! We evaluated the performance of our method against three other leading contemporary heuristic methods: Huff's Slack Scheduling, Wang, Eisenbeis, Jourdan and Su's FRLC, and Gasperoni and Schwiegelshohn's modified list scheduling. Experimental results show that the method described in this paper performed significantly better than these methods.