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Biomedical subjects

A D Jackson

Publications and source records attributed to A D Jackson.

At least 19 recordsLinked to original sources

Citation networks in high energy physics.

The citation network constituted by the SPIRES database is investigated empirically. The probability that a given paper in the SPIRES database has k citations is well described by simple power laws, P(k) proportional to k(-alpha), with alpha approximately 1.2 for k less than 50 citations and alpha approximately 2.3 for 50 or more citations. A consideration of citation distribution by subfield shows that the citation patterns of high energy physics form a remarkably homogeneous network. Further, we utilize the knowledge of the citation distributions to demonstrate the extreme improbability that the citation records of selected individuals and institutions have been obtained by a random draw on the resulting distribution.

Journal Article↗

Products of random matrices.

We derive analytic expressions for infinite products of random 2 x 2 matrices. The determinant of the target matrix is log-normally distributed, whereas the remainder is a surprisingly complicated function of a parameter characterizing the norm of the matrix and a parameter characterizing its skewness. The distribution may have importance as an uncommitted prior in statistical image analysis.

Journal Article↗

Lieb mode in a quasi-one-dimensional bose-einstein condensate of atoms.

We calculate the dispersion relation associated with a solitary wave in a quasi-one-dimensional Bose-Einstein condensate of atoms confined in a harmonic, cylindrical trap in the limit of weak and strong interactions. In both cases, the dispersion relation is linear for long-wavelength excitations and terminates at the point where the group velocity vanishes. We also calculate the dispersion relation of sound waves in both limits of weak and strong coupling.

Journal Article↗

Random matrix theory and acoustic resonances in plates with an approximate symmetry.

We discuss a random matrix model of systems with an approximate symmetry and present the spectral fluctuation statistics and eigenvector characteristics for the model. An acoustic resonator like, e.g., an aluminum plate may have an approximate symmetry. We have measured the frequency spectrum and the widths for acoustic resonances in thin aluminum plates, cut in the shape of the so-called three-leaf clover. Due to the mirror symmetry through the middle plane of the plate, each resonance of the plate belongs to one of two mode classes and we show how to separate the modes into these two classes using their measured widths. We compare the spectral statistics of each mode class with results for the Gaussian orthogonal ensemble. By cutting a slit of increasing depth on one face of the plate, we gradually break the mirror symmetry and study the transition that takes place as the two classes are mixed. Presenting the spectral fluctuation statistics and the distribution of widths for the resonances, we find that this transition is well described by the random matrix model.

Journal Article↗

Weakly interacting Bose-Einstein condensates under rotation: mean-field versus exact solutions.

We consider a weakly interacting, harmonically trapped Bose-Einstein condensed gas under rotation and investigate the connection between the energies obtained from mean-field calculations and from exact diagonalizations in a subspace of degenerate states. From the latter we derive an approximation scheme valid in the thermodynamic limit of many particles. Mean-field results are shown to emerge as the correct leading-order approximation to exact calculations in the same subspace.

Journal Article↗

Airway goblet-cell mucus secretion.

A mucus hypersecretory phenotype is a dominant characteristic of chronic airways diseases such as chronic bronchitis and asthma. This phenotype develops following chronic exposure of the respiratory tract to particulate matter, allergens, irritants and/or pathogens. The associated increase in the mucus-producing potential of the respiratory epithelium represents an innate host response that can be modulated by elements of the adaptive host response. Although elevation of mucus production is designed to protect the airways, increasing evidence suggests that in excess it can be detrimental to health. Considerable progress has been made over the past five years in understanding the mechanisms involved in the development and regulation of the hypersecretory phenotype. This progress has set the stage for the development of successful dedicated mucomodulatory strategies to counter the negative impact of excess mucus production in respiratory disease.

Animals↗

Genetic survival analysis of age-at-onset of bipolar disorder: evidence for anticipation or cohort effect in families.

Age-at-onset (AAO) in a number of extended families ascertained for bipolar disorder was analysed using survival analysis techniques, fitting proportional hazards models to estimate the fixed effects of sex, year of birth, and generation, and a random polygenic genetic effect. Data comprised the AAO (for 171 affecteds) or age when last seen (ALS) for 327 unaffecteds, on 498 individuals in 27 families. ALS was treated as the censored time in the statistical analyses. The majority of individuals classified as affected were diagnosed with bipolar I and II (n = 103) or recurrent major depressive disorder (n = 68). In addition to the significant effects of sex and year of birth, a fitted 'generation' effect was highly significant, which could be interpreted as evidence for an anticipation effect. The risk of developing bipolar or unipolar disorder increased twofold with each generation descended from the oldest founder. However, although information from both affected and unaffected individuals was used to estimate the relative risk of subsequent generations, it is possible that the results are biased because of the 'Penrose effect'. Females had a twofold increased risk in developing depressive disorder relative to males. The risk of developing bipolar or unipolar disorder increased by approximately 4% per year of birth. A polygenic component of variance was estimated, resulting in a 'heritability' of AAO of approximately 0.52. In a family showing strong evidence of linkage to chromosome 4p (family 22), the 'affected haplotype' increased the relative risk of being affected by a factor of 46. In this family, there was strong evidence of a time trend in the AAO. When either year of birth or generation was fitted in the model, these effects were highly significant, but neither was significant in the presence of the other. For this family, there was no increase in trinucleotide repeats measured by the repeat expansion detection method in affected individuals compared with control subjects. Proportional hazard models appear appropriate to analyse AAO data, and the methodology will be extended to map quantitative trait loci (QTL) for AAO.

Adult↗

Analytical results for the interaction energy of a trapped, weakly interacting Bose-Einstein condensate.

We examine the problem of a repulsive, weakly interacting and harmonically trapped Bose-Einstein condensate under rotation. We derive a simple analytic expression for the energy incorporating the interactions when the angular momentum per particle is between zero and one and find that the interaction energy decreases linearly as a function of the angular momentum in agreement with previous numerical and limiting analytical studies.

Journal Article↗

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.

Adrenergic beta-Agonists↗

The effect of mutations in genes required for lipopolysaccharide synthesis on Haemophilus influenzae type b colonization of human nasopharyngeal tissue.

Haemophilus influenzae type b (Hib) is an upper respiratory tract commensal that can cause invasive disease, particularly in young children. Lipopolysaccharide (LPS) has been implicated as a major virulence determinant of Hib, and changes in LPS structure may influence bacterial interactions with the respiratory mucosa. We have examined the effect of variations in LPS on the interaction of Hib with human nasal turbinate tissue maintained in an organ culture model with an air-interface, by using isogenic derivatives of strains RM153 (Eagan) and RM7004 expressing truncated LPS due to mutations in genes contained within the chromosomal loci lic1 and lic2 (lic1lic2) or in the galE and galK genes (galEK). Tissue was infected with an inoculating dose of 2.3-3.3 x 10(6) colony forming units (cfu) in 2 microliters of PBS and maintained for 24 h. By scanning electron microscopy the percentage of the organ culture surface exhibiting epithelial damage increased from 5.3 +/- 1.4 in controls to 12.5 +/- 6.4-26.3 +/- 9.1 following infection, with no significant difference between parent strains and their derivatives. There was significant bacterial tropism for mucus, and to a lesser extent damaged cells, which was not influenced by the LPS phenotype. All strains caused separation of epithelial cells, adhered to non-luminal cell surfaces, and invaded the epithelium intercellularly. We conclude that Hib associated with mucus and damaged epithelium, and infrequently with normal epithelium, but changes in the LPS phenotype did not affect the interaction between Hib and the mucosal surface of human nasal turbinate tissue.

Bacterial Adhesion↗

Comparison of haemophilus influenzae type b interaction with respiratory mucosa organ cultures maintained with an air interface or immersed in medium.

Haemophilus influenzae type b infection of immersed and air interface organ cultures for 24 h caused significant epithelial damage. Bacterial association with mucus, damaged epithelium, and unciliated cells was significantly higher in air interface than immersed organ cultures, and total bacterial association was 55.8 times greater. Bacteria exhibited tropism for mucus only on explants maintained with an air interface. We conclude that immersion of nasopharyngeal tissue in medium may influence bacterial interaction with the mucosal surface.

Culture Media↗

A human respiratory-tissue organ culture incorporating an air interface.

The immersion of respiratory tissue in organ cultures is unphysiologic and may influence the interactions of the tissue with experimental agents. We have assessed an organ culture of human nasal turbinate tissue with an air interface by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), with and without replacement of culture medium. Without replacement of medium, ciliary beat frequency (CBF) was normal (11.3 +/- 0.5 Hz) at 5 d, but fell significantly (p<0.05) to 7.9 +/- 0.8 Hz at 10 d. The degree of ciliation decreased significantly (p<0.05) at 4 and 10 d. Nuclear heterochromatin in all cell types was significantly (p<0.05) reduced at 5 d. Significant (p<0.05) mitochondrial abnormalities occurred in ciliated cells at 5 d and in both ciliated and unciliated cells at 10 d. With daily replacement of medium, CBF fell significantly (p<0.05) from 11.6 +/- 0.2 Hz at Time 0 to 10.6 +/- 0.3 Hz after 20 d. The proportions of ciliated and nonciliated cells did not change after 20 d, but the proportion of mucus cells was higher at 20 d (26.3 +/- 5.4%) than at Time 0 (9.8 +/- 2.7%). No mitochondrial abnormalities, changes in nuclear heterochromatin levels, or reduction in cilial density on ciliated cells were present. The amount of damaged epithelium was less at 20d (7.2 +/- 3.8%) than at Time 0 (19.0 +/- 5.8%). This model more closely reproduces physiologic conditions in vitro than do models involving the immersion of respiratory tissue in media. Its long viability will permit studies of virus and bacterial infections, and of the effects of pharmacologic agents and environmental factors.

Air↗

The biology of bacterial colonization and invasion of the respiratory mucosa.

Despite being regularly exposed to particulate matter during breathing, which contains bacteria from the commensal flora in the nasopharynx and from the environment, the healthy lung is kept sterile by efficient defence mechanisms. Bacterial infections of the respiratory mucosa represent a dynamic interaction, to which both host and bacterial factors contribute. The abnormal host defences associated with chronic respiratory infections (e.g. cystic fibrosis and other forms of bronchiectasis) serve to emphasize their permissive role. The bacteria that cause bronchial infections possess a wide array of potential virulence factors that contribute to their pathogenicity. Many of these factors influence the mucociliary system, an important first-line defence mechanism. The multiplication, spread and persistence of bacteria within the bronchial lumen, and consequent damage to the epithelium, stimulates a chronic inflammatory response, which also impairs mucociliary clearance and damages lung tissue. A greater understanding of host-bacterial interactions during mucosal infections should in the future lead to the development of new therapies and treatment strategies.

Animals↗