Showing papers by "Queen's University published in 1996"

Numerical distribution functions for unit root and cointegration tests

Abstract: SUMMARY This paper employs response surface regressions based on simulation experiments to calculate distribution functions for some well-known unit root and cointegration test statistics. The principal contributions of the paper are a set of data files that contain estimated response surface coefficients and a computer program for utilizing them. This program, which is freely available via the Internet, can easily be used to calculate both asymptotic and finite-sample critical values and P-values for any of the tests. Graphs of some of the tabulated distribution functions are provided. An empirical example deals with interest rates and inflation rates in Canada. Tests of the null hypothesis that a time-series process has a unit root have been widely used in recent years, as have tests of the null hypothesis that two or more integrated series are not cointegrated. The most commonly used unit root tests are based on the work of Dickey and Fuller (1979) and Said and Dickey (1984). These are known as Dickey-Fuller (DF) tests and Augmented Dickey-Fuller (ADF) tests, respectively. These tests have non-standard distributions, even asymptotically. The cointegration tests developed by Engle and Granger (1987) are closely related to DF and ADF tests, but they have different, non-standard distributions, which depend on the number of possibly cointegrated variables. Although the asymptotic theory of these unit root and cointegration tests is well developed, it is not at all easy for applied workers to calculate the marginal significance level, or P-value, associated with a given test statistic. Until a few years ago (MacKinnon, 1991), accurate critical values for cointegration tests were not available at all. In a recent paper (MacKinnon, 1994), I used simulation methods to estimate the asymptotic distributions of a large number of unit root and cointegration tests. I then obtained reasonably simple approximating equations that may be used to obtain approximate asymptotic P-values. In the present paper, I extend the results to allow for up to 12 variables, instead of six, and I correct two deficiencies of the earlier work. The first deficiency is that the approximating equations are considerably less accurate than the underlying estimated asymptotic distributions. The second deficiency is that, even though the simulation experiments provided information about the finite-sample distributions of the test statistics, the approximating equations were obtained only for the asymptotic case. The key to overcoming these two deficiencies is to use tables of response surface coefficients, from which estimated quantiles for any sample size may be calculated, instead of equations to

Numerical Distribution Functions of Likelihood Ratio Tests for Cointegration

Abstract: This paper employs response surface regressions based on simulation experments to calculate asymptotic distribution functions for the likelihood ratio tests for cointegration proposed by Johansen The paper provides tables of critical values that are very much more accurate than those available previously However the principal contributions of the paper are a set of data les that contain estimated asymptotic quantiles obtained from response surface estimation and a computer program for utilizing them This program which is freely available via the Internet can easily be used to calculate asymptotic critical values and P values Graphs of some of the tabulated distribution functions are also provided An empirical example motivated by the European Economic and Monetary Union proposed in the Maastricht Treaty suggests that not all the countries of the European Union may qualify initially for participation in the EMU.

Effects of Transformational Leadership Training on Attitudinal and Financial Outcomes: A Field Experiment

Abstract: A pretest-posttest control-group design (N = 20) was used to assess the effects of transformational leadership training, with 9 and 11 managers assigned randomly to training and control groups, respectively. Training consisted of a 1-day group session and 4 individual booster sessions thereafter on a monthly basis. Multivariate analyses of covariance, with pretest scores as the covariate, showed that the training resulted in significant effects on subordinates' perceptions of leaders' transformational leadership, subordinates' own organizational commitment, and 2 aspects of branch-level financial performance.

The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.

Abstract: Objective. —Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design. —Correlative survey study of 477 MEN 2 families. Setting. —Eighteen tertiary referral centers worldwide. Patients. —A total of 477 independent MEN 2 families. Main Outcome Measures. —Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results. —There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B-specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions. —This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.

The organization and regulation of plant glycolysis

Abstract: This review discusses the organization and regulation of the glycolytic pathway in plants and compares and contrasts plant and nonplant glycolysis. Plant glycolysis exists both in the cytosol and plastid, and the parallel reactions are catalyzed by distinct nuclear-encoded isozymes. Cytosolic glycolysis is a complex network containing alternative enzymatic reactions. Two alternate cytosolic reactions enhance the pathway's ATP yield through the use of pyrophosphate in place of ATP. The cytosolic glycolytic network may provide an essential metabolic flexibility that facilitates plant development and acclimation to environmental stress. The regulation of plant glycolytic flux is assessed, with a focus on the fine control of enzymes involved in the metabolism of fructose-6-phosphate and phosphoenolpyruvate. Plant and nonplant glycolysis are regulated from the "bottom up" and "top down," respectively. Research on tissue- and developmental-specific isozymes of plant glycolytic enzymes is summarized. Potential pitfalls associated with studies of glycolytic enzymes are considered. Some glycolytic enzymes may be multifunctional proteins involved in processes other than carbohydrate metabolism.

Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.

Abstract: Objective: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. Design: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. Setting: Hospital and community based casecontrol and cohort studies. Main outcome measures: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. Results: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. Conclusions: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs. Key messages Because there are no important differences in efficacy, choice of first line treatment with these drugs should be based on their relative toxicity Meta-analysis of the available epidemiological studies shows wide differences between individual drugs in the risk of inducing gastrointestinal bleed- ing and ulcer perforation Of the drugs in common use, ibuprofen and diclofenac rank low in toxicity whereas azapropa- zone, ketoprofen, and piroxicam rank high Some of the differences between drugs may be explained by dose, and the advantage of “low risk” drugs may be lost once their dose is increased

Muscle creatine loading in men

Abstract: The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.

A full genome search in multiple sclerosis

Abstract: The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Mechanism of Optically Inscribed High-Efficiency Diffraction Gratings in Azo Polymer Films

Abstract: A series of amorphous azobenzene-containing polymers were cast as thin films and shown to produce both reversible volume diffraction gratings and high-efficiency surface gratings by laser irradiation at an absorbing wavelength. The latter process involves localized mass transport of the polymer chains to a high degree, as atomic force microscopy reveals surface profile depths near that of the original film thickness. A mechanism for this phenomenon is proposed which involves pressure gradients as a driving force, present due to different photochemical behaviors of the azo chromophores at different regions of the interference pattern. The phase addition of the two beams in the interference pattern leads to regions of high trans-cis-trans isomerization by the absorbing azo groups, bordered by regions of low isomerization. As the geometrical isomerization requires free volume in excess of that available in the cast films, the photochemical reaction in these areas produces a laser-induced internal pressure ab...

Cellular and Molecular Actions of Juvenile Hormone. II. Roles of Juvenile Hormone in Adult Insects

Abstract: Publisher Summary Among animal hormones, juvenile hormone (JH) is distinctive because of its unique structure and the diversity of its effects on insect development and reproduction. This chapter reviews the actions of JH on the fat body, gonads, accessory glands, muscle, and nervous system of adult insects. Whereas the epidermis is a major target of premetamorphic JH action, it has been studied little in adult insects, which generally do not moult. However, since the development of yellow pigmentation that accompanies sexual maturation in adult male locusts is clearly dependent on JH-regulation processes, in which cellular and molecular mechanism are investigated. The rapid recent progress in understanding how ecdysteroids regulate the gene activities has resulted from the opportunities afforded by drosophila melanogaster: mapped and characterized mutants, polytene chromosomes with puffs marking active genes, efficient germ-line transformation. The recognition of two aspects of JH action in the tissues of adult insects is reviewed. A model for understanding some aspects of priming by JH may be found in the action of ecdysteroids, where early genes produce factors needed for the expression of late genes. In structure, thyroxine is very different from JH, but there is considerable resemblance between thyroxine and phenoxyphenoxy carbamate, fenoxycarb. Functionally, there are marked similarities. Thyroxine governs metamorphosis in amphibians, but is remarkably pleiotropic in governing many processes ranging from the maturation of the central nervous system to thermoregulation. The chapter emphasizes the importance of selecting insect systems on the basis of their optimal features for research, rather than historical precedent or economic importance. With selection of appropriate systems and application of the cell and molecular research techniques now available, the elusive problem of JH action should soon yield to enlightenment.

Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa.

Abstract: OprJ, overproduced in nfxB multidrug-resistant strains of Pseudomonas aeruginosa, and OprK, overproduced in the multidrug-resistant strain K385, were demonstrated to be immunologically cross-reactive using an OprJ-specific monoclonal antibody. Treatment of the purified proteins with trypsin or chymotrypsin yielded virtually indistinguishable digestion patterns, and the N-terminal sequence of two trypsin fragments was identical for both proteins, indicating that OprJ and OprK share identity. The N-terminal amino acid sequences were used to facilitate cloning of the oprJ gene on a 5kbp Kpnl fragment and a 10 kbp BamHl fragment. Nucleotide sequencing of portions of these fragments revealed that oprJ was the terminal gene in a putative three-gene operon, mexC-mexD-oprJ. The predicted mexC-mexD-oprJ gene products exhibit homology to the MexA-MexB-OprM components of the multidrug-resistance efflux pump of P. aeruginosa (43-46% identity). Consistent with an implied role for mexC-mexD-oprJ in drug efflux, the mexC-mexD-oprJ-hyperexpressing strain K385 showed reduced accumulation of a variety of antibiotics as compared with its parent strain, and this drug 'exclusion' was abrogated by energy inhibitors. The mexC and oprJ products are putative lipoproteins of a molecular mass of 40,707 and 51,742 Da, respectively, while mexD was predicted to encode a protein of 111 936 Da. Sequencing upstream of mexC revealed the presence of the nfxB gene transcribed divergently from the efflux genes. Overproduction of OprJ and the attendant multiple-antibiotic resistance of strain K385 was shown to result from a point mutation in nfxB, resulting in a H87-->R change in the predicted NfxB polypeptide. OprJ overproduction and multidrug resistance in K385 was reversed by the cloned nfxB gene, suggesting that nfxB encodes a repressor of mexC-mexD-oprJ expression. Consistent with this, the cloned nfxB gene repressed synthesis of a mexC-lacZ fusion in Escherichia coli. nfxB also repressed expression of a nfxB-lacZ fusion, indicating that NfxB negatively regulates its own expression. These data indicate that the multidrug resistance of nfxB strains is due to overexpression of an efflux operon, mexC-mexD-oprJ, encoding components of a second efflux pump in P. aeruginosa.

Clinical studies of multiple endocrine neoplasia type 1 (MEN1)

Abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.

Regression Models: Censored, Sample Selected, or Truncated Data

Abstract: What techniques can social scientists use when an outcome variable for a sample is not representative of the population for whom they would like to generalize the results? This book provides an introduction to regression models for such data including censored, sample-selected and truncated data.

Temporal constraints on the McGurk effect

Abstract: Three experiments are reported on the influence of different timing relations on the McGurk effect. In the first experiment, it is shown that strict temporal synchrony between auditory and visual speech stimuli is not required for the McGurk effect. Subjects were strongly influenced by the visual stimuli when the auditory stimuli lagged the visual stimuli by as much as 180 msec. In addition, a stronger McGurk effect was found when the visual and auditory vowels matched. In the second experiment, we paired auditory and visual speech stimuli produced under different speaking conditions (fast, normal, clear). The results showed that the manipulations in both the visual and auditory speaking conditions independently influenced perception. In addition, there was a small but reliable tendency for the better matched stimuli to elicit more McGurk responses than unmatched conditions. In the third experiment, we combined auditory and visual stimuli produced under different speaking conditions (fast, clear) and delayed the acoustics with respect to the visual stimuli. The subjects showed the same pattern of results as in the second experiment. Finally, the delay did not cause different patterns of results for the different audiovisual speaking style combinations. The results suggest that perceivers may be sensitive to the concordance of the time-varying aspects of speech but they do not require temporal coincidence of that information.

The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Abstract: Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump

Abstract: We have previously shown that the multidrug resistance protein (MRP) mediates the ATP-dependent membrane transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) and of structurally related anionic conjugates of lipophilic compounds [Jedlitschky, Leier, Buchholz, Center and Keppler (1994) Cancer Res. 54, 4833-4836; Leier, Jedlitschky, Buchholz, Cole, Deeley and Keppler (1994) J. Biol. Chem. 269, 27807-27810]. We demonstrate in the present study that MRP also mediates the ATP-dependent transport of GSSG, as shown in membrane vesicles from human leukaemia cells overexpressing MRP (HL60/ADR cells) or HeLa cells transfected with an MRP expression vector (HeLa T5 cells) in comparison with the respective parental or control cells. The Km value for ATP-dependent transport of GSSG was 93 +/- 26 microM (mean value +/- S.D., n=5) in membrane vesicles from HeLa T5 cells. GSH, at a concentration of 100 microM, was not a substrate for any significant ATP-dependent MRP-mediated transport. The transport of GSSG was competitively inhibited by LTC4, by the leukotriene D4 receptor antagonist 3-([?3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl?-?(3-dimethylamino-3- oxopropyl)-thio?-methyl]thio)propanoic acid (MK 571) and by S-decylglutathione, with K1 values of 0.3, 0.6 and 0.7 microM respectively. These studies identify MRP as the membrane glycoprotein which mediates the ATP-dependent export of GSSG from these cells.

Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men

Abstract: Ross, Robert, John Rissanen, Heather Pedwell, Jennifer Clifford, and Peter Shragge. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 24...

Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression.

Abstract: The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB-oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified. The predicted MexR product contains 147 amino acids with a molecular mass of 16,964 Da, which is consistent with the observed size of the overexpressed mexR gene product. MexR was homologous to MarR, the repressor of MarA-dependent multidrug resistance in Escherichia coli, and other repressors of the MarR family. A mexR knockout mutant showed a twofold increase in expression of both plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+ parent strain, indicating that the mexR gene product negatively regulates expression of the mexA-mexB-oprM operon. Furthermore, the cloned mexR gene product reduced expression of a plasmid-borne mexA-lacZ fusion in E. coli, indicating that MexR represses mexA-mexB-oprM expression directly. Consistent with the increased expression of the efflux operon in the mexR mutant, the mutant showed an increase (relative to its MexR+ parent) in resistance to several antimicrobial agents. Expression of a mexR-lacZ fusion increased threefold in a mexR knockout mutant, indicating that mexR is negatively autoregulated. OCR1, a nalB multidrug-resistant mutant which overproduces OprM, exhibited a greater than sevenfold increase in expression of a chromosomal mexA-phoA fusion compared with its parent. Introduction of a mexR knockout mutation in strain OCR1 eliminated this increase in efflux gene expression and, as expected, increased the susceptibility of the strain to a variety of antibiotics. The nucleotide sequences of the mexR genes of OCR1 and its parental strain revealed a single base substitution in the former which would cause a predicted substitution of Trp for Arg at position 69 of its mexR product. These data suggest that MexR possesses both repressor and activator function in vivo, the activator form being favored in nalB multidrug-resistant strains.