Vergence analysis reveals the influence of axial distances on accommodation with age and axial ametropia

Despite numerous investigations, the aetiology and mechanism of accommodation and presbyopia remains equivocal. Using Gaussian first-order ray tracing calculations, we examine the contribution that ocular axial distances make to the accommodation response. Further, the influence of age and ametropia are also considered. The data show that all changes in axial distances during accommodation reduce the accommodation response, with the reduction in anterior chamber depth contributing most to this overall attenuation. Although the total power loss due to the changes in axial distances remained constant with increasing age, hyperopes exhibited less accommodation than myopes. The study, therefore, enhances our understanding of biometric accommodative changes and demonstrates the utility of vergence analysis in the assessment of accommodation.

Drug targeting with phagocytic polymorphonuclear leucocytes

1. Phagocytic polymorphonuclear leucocytes (PMNLs) or neutrophils have a marked avidity for the uptake of particulate material and are the first cell type to respond to inflammatory stimuli in vivo. 2. By harnessing these pathophysiological characteristics the inherent targeting capacity of the PMNL could be exploited to carry drug loaded particles to these sites. 3. In vitro chemotaxis of PMNLs was studied in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in the Blindwell chamber assay. 4. After phagocytosis of 1.1m polystyrene latex (PSL) beads at a range of incubation concentrations (5,10,20, and 30 beads/cell) the migration of the PMNL population was not significantly different from control, without beads. 5. The distribution of the beads within the filter showed that a disproportionately large number of PSL (50%) were associated with the cells on the surface of the filter that had not penetrated the filter. Eighty per cent of the PMNL population migrated and despite containing less PSL beads/cell, 50% of the dose was carried into the filter. Between 5 and 10% of these PSL were carried beyond 60m in the assay. 6. These results suggested heterogeneity of the PMNL population and to achieve efficient targeting with these cells preferential selection of the migratory sub-population would be needed. 7. The air-pouch model was then developed to study the focal accumulation of PMNLs in vivo. The PMNL isolated did not survive long enough in the circulation due to the trauma of the isolation procedure used; an alternative method will have to be employed.

The geochemistry and petrogenesis of the minor intrusive suite associated with the late Caledonian Criffell-Dalbeattie pluton, SW Scotland

The Criffell-Dalbeattie pluton from SW Scotland is one of a suite of late Caledonian granitoids which are associated with extensive, contemporaneous and compositionally diverse suits of minor intrusions. The minor intrusive suite associated with the Criffell-Dalbeattie pluton is dominantly composed of a series of porphyritic microdiorites, microgranodiorites and microgranites known collectively as the porphyrite-porphyry series. This series can be divided into two groups, the porphyrites and the quartz porphyries, on the basis of petrography and geochemistry although there is some compositional overlap between the two. Compositionally, the porphyrites and quartz porphyries appear to correspond to the granodiorites and granites, respectively, which comprise the Criffell-Dalbeattie pluton, suggesting that the porphyrite-porphyry series of dykes represent magmas which were tapped from the evolving granitic magma chamber. The most mafic component of the minor intrusive suite is represented by calc-alkaline hornblende- and mica bearing lamprophyres. Geochemical studies, including fractional crystallisation, combine assimilation-fractional crystallisation (AFC) show that these are mafic, LILE and LREE enriched melts derived by low degrees of partial melting of a subduction-modified mantle source. It is suggested that the source of the lamprophyres is "Lake District" lithosphere, metasomatised by Lower Palaeozoic subduction, and thrust under the southern part of the Southern Uplands. AFC modelling using chemical and isotopic data further suggest that there is a close genetic link between the lamprophyres and the Criffell-Dalbeattie granitoids and that lamprophyres represent the mantle derived precursors of the Criffell-Dalbeattie granitoids.

Comparison of techniques for measuring anterior chamber depth:Orbscan imaging, Smith's technique, and van Herick's method

Background Evaluation of anterior chamber depth (ACD) can potentially identify those patients at risk of angle-closure glaucoma. We aimed to: compare van Herick’s limbal chamber depth (LCDvh) grades with LCDorb grades calculated from the Orbscan anterior chamber angle values; determine Smith’s technique ACD and compare to Orbscan ACD; and calculate a constant for Smith’s technique using Orbscan ACD. Methods Eighty participants free from eye disease underwent LCDvh grading, Smith’s technique ACD, and Orbscan anterior chamber angle and ACD measurement. Results LCDvh overestimated grades by a mean of 0.25 (coefficient of repeatability [CR] 1.59) compared to LCDorb. Smith’s technique (constant 1.40 and 1.31) overestimated ACD by a mean of 0.33 mm (CR 0.82) and 0.12 mm (CR 0.79) respectively, compared to Orbscan. Using linear regression, we determined a constant of 1.22 for Smith’s slit-length method. Conclusions Smith’s technique (constant 1.31) provided an ACD that is closer to that found with Orbscan compared to a constant of 1.40 or LCDvh. Our findings also suggest that Smith’s technique would produce values closer to that obtained with Orbscan by using a constant of 1.22.

Shape of the posterior vitreous chamber in human emmetropia and myopia

PURPOSE - To compare posterior vitreous chamber shape in myopia to that in emmetropia. METHODS - Both eyes of 55 adult subjects were studied, 27 with emmetropia (MSE =-0.55; <+0.75D; mean +0.09 ±0.36D) and 28 with myopia (MSE -5.87 ±2.31D). Cycloplegic refraction was measured with a Shin Nippon autorefractor and anterior chamber depth and axial length with a Zeiss IOLMaster. Posterior vitreous chamber shapes were determined from T2-weighted MRI (3-Tesla) using procedures previously reported by our laboratory. 3-D surface model coordinates were assigned to nasal, temporal, superior and inferior quadrants and plotted in 2-D to illustrate the composite shape of respective quadrants posterior to the second nodal point. Spherical analogues of chamber shape were constructed to compare relative sphericity between refractive groups and quadrants. RESULTS - Differences in shape occurred in the region posterior to points of maximum globe width and were thus in general accord with an equatorial model of myopic expansion. Shape in emmetropia is categorised distinctly as that of an oblate ellipse and in myopia as an oblate ellipse of significantly less degree such that it approximates to a sphere. There was concordance between shape and retinotopic projection of respective quadrants into right, left, superior and inferior visual fields. CONCLUSIONS - The transition in shape from oblate ellipse to sphere with axial elongation supports the hypothesis that myopia may be a consequence of equatorial restriction associated with biomechanical anomalies of the ciliary apparatus. The synchronisation of quadrant shapes with retinotopic projection suggests that binocular growth is coordinated by processes that operate beyond the optic chiasm.

Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.

Factors preventing myopia progression with orthokeratology correction

PURPOSE: To examine which baseline measurements constitute predictive factors for axial length growth over 2 years in children wearing orthokeratology contact lenses (OK) and single-vision spectacles (SV). METHODS: Sixty-one children were prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The primary outcome measure (dependent variable) was axial length change at 2 years relative to baseline. Other measurements (independent variables) were age, age of myopia onset, gender, myopia progression 2 years before baseline and baseline myopia, anterior chamber depth, corneal power and shape (p value), and iris and pupil diameters as well as parental refraction. The contribution of all independent variables to the 2-year change in axial length was assessed using univariate and multivariate regression analyses. RESULTS: After univariate analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia (all p < 0.05). In multivariate analyses, older age and greater corneal power were associated with smaller increases in axial length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris diameter was associated with smaller increases in axial length (p = 0.021). CONCLUSIONS: Orthokeratology is a successful treatment option in controlling axial elongation compared to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia. © American Academy of Optometry.

Refractive and biometric changes with silicone hydrogel contact lenses

Purpose. This study reports data from an 18-month longitudinal study of neophyte contact lens wearers and compares changes in ocular refraction and biometry induced by daily wear and continuous wear of two different silicone hydrogel (SiH) materials. Methods. Forty-five subjects were enrolled in the study and randomly assigned to wear one of the two silicone hydrogel materials: Lotrafilcon A or Balafilcon A lenses on either a daily or continuous wear basis. Measurements of objective refraction, axial length, anterior chamber depth, corneal curvature, and the rate of peripheral corneal flattening were performed before and 1, 3, 6, 12, and 18 months after initial fitting. Results. Mean spherical equivalent refractive error increased in the myopic direction in all contact lens groups across time (p < 0.001). Axial length was the main biometric contributor to the development of myopia. After 18 months of lens wear, subjects in the Lotrafilcon A group showed the greater mean increase in myopia (i.e., -0.50 D). Conclusions. The results of this study show that increases in myopia, similar if not higher than those found to occur normally in young adult noncontact lens wearers, still occur with silicone hydrogel contact lens wear. The main biometric contributor to the progression of myopia was an increase in axial length. Differences between our results and those of previous studies with silicone hydrogel contact lenses could be attributed to the differing populations used in which both age and occupation may have played a role. Copyright © 2005 American Academy of Optometry.

IL-8 released constitutively by primary bronchial epithelial cells in culture forms an inactive complex with secretory component

The bronchial epithelium is a source of both α and β chemokines and, uniquely, of secretory component (SC), the extracellular ligand-binding domain of the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and α2-macroglobulin, bind IL-8. Therefore, we tested the hypothesis that SC binds IL-8, modifying its activity as a neutrophil chemoattractant. Primary bronchial epithelial cells were cultured under conditions to optimize SC synthesis. The chemokines IL-8, epithelial neutrophil-activating peptide-78, growth-related oncogene α, and RANTES were released constitutively by epithelial cells from both normal and asthmatic donors and detected in high m.w. complexes with SC. There were no qualitative differences in the production of SC-chemokine complexes by epithelial cells from normal or asthmatic donors, and in all cases this was the only form of chemokine detected. SC contains 15% N-linked carbohydrate, and complete deglycosylation with peptide N-glycosidase F abolished IL-8 binding. In micro-Boyden chamber assays, no IL-8-dependent neutrophil chemotactic responses to epithelial culture supernatants could be demonstrated. SC dose-dependently (IC50 ∼0.3 nM) inhibited the neutrophil chemotactic response to rIL-8 (10 nM) in micro-Boyden chamber assays and also inhibited IL-8-mediated neutrophil transendothelial migration. SC inhibited the binding of IL-8 to nonspecific binding sites on polycarbonate filters and endothelial cell monolayers, and therefore the formation of haptotactic gradients, without effects on IL-8 binding to specific receptors on neutrophils. The data indicate that in the airways IL-8 may be solubilized and inactivated by binding to SC

Algorithms for scheduling parallel batch processing machines with non-identical job ready times

This research is motivated by a practical application observed at a printed circuit board (PCB) manufacturing facility. After assembly, the PCBs (or jobs) are tested in environmental stress screening (ESS) chambers (or batch processing machines) to detect early failures. Several PCBs can be simultaneously tested as long as the total size of all the PCBs in the batch does not violate the chamber capacity. PCBs from different production lines arrive dynamically to a queue in front of a set of identical ESS chambers, where they are grouped into batches for testing. Each line delivers PCBs that vary in size and require different testing (or processing) times. Once a batch is formed, its processing time is the longest processing time among the PCBs in the batch, and its ready time is given by the PCB arriving last to the batch. ESS chambers are expensive and a bottleneck. Consequently, its makespan has to be minimized. ^ A mixed-integer formulation is proposed for the problem under study and compared to a formulation recently published. The proposed formulation is better in terms of the number of decision variables, linear constraints and run time. A procedure to compute the lower bound is proposed. For sparse problems (i.e. when job ready times are dispersed widely), the lower bounds are close to optimum. ^ The problem under study is NP-hard. Consequently, five heuristics, two metaheuristics (i.e. simulated annealing (SA) and greedy randomized adaptive search procedure (GRASP)), and a decomposition approach (i.e. column generation) are proposed—especially to solve problem instances which require prohibitively long run times when a commercial solver is used. Extensive experimental study was conducted to evaluate the different solution approaches based on the solution quality and run time. ^ The decomposition approach improved the lower bounds (or linear relaxation solution) of the mixed-integer formulation. At least one of the proposed heuristic outperforms the Modified Delay heuristic from the literature. For sparse problems, almost all the heuristics report a solution close to optimum. GRASP outperforms SA at a higher computational cost. The proposed approaches are viable to implement as the run time is very short. ^

Parameter optimization for noise and vibration reduction associated with position and speed sensorless control of permanent magnet machines at low speed

With the advantages and popularity of Permanent Magnet (PM) motors due to their high power density, there is an increasing incentive to use them in variety of applications including electric actuation. These applications have strict noise emission standards. The generation of audible noise and associated vibration modes are characteristics of all electric motors, it is especially problematic in low speed sensorless control rotary actuation applications using high frequency voltage injection technique. This dissertation is aimed at solving the problem of optimizing the sensorless control algorithm for low noise and vibration while achieving at least 12 bit absolute accuracy for speed and position control. The low speed sensorless algorithm is simulated using an improved Phase Variable Model, developed and implemented in a hardware-in-the-loop prototyping environment. Two experimental testbeds were developed and built to test and verify the algorithm in real time.^ A neural network based modeling approach was used to predict the audible noise due to the high frequency injected carrier signal. This model was created based on noise measurements in an especially built chamber. The developed noise model is then integrated into the high frequency based sensorless control scheme so that appropriate tradeoffs and mitigation techniques can be devised. This will improve the position estimation and control performance while keeping the noise below a certain level. Genetic algorithms were used for including the noise optimization parameters into the developed control algorithm.^ A novel wavelet based filtering approach was proposed in this dissertation for the sensorless control algorithm at low speed. This novel filter was capable of extracting the position information at low values of injection voltage where conventional filters fail. This filtering approach can be used in practice to reduce the injected voltage in sensorless control algorithm resulting in significant reduction of noise and vibration.^ Online optimization of sensorless position estimation algorithm was performed to reduce vibration and to improve the position estimation performance. The results obtained are important and represent original contributions that can be helpful in choosing optimal parameters for sensorless control algorithm in many practical applications.^

Musical commonplace book : manuscript, [approximately 1790-approximately 1810]

Contains songs, partly from English operas, and instrumental music.

Engineering Highly-functional, Self-regenerative Skeletal Muscle Tissues with Enhanced Vascularization and Survival in Vivo

Tissue engineering of biomimetic skeletal muscle may lead to development of new therapies for myogenic repair and generation of improved in vitro models for studies of muscle function, regeneration, and disease. For the optimal therapeutic and in vitro results, engineered muscle should recreate the force-generating and regenerative capacities of native muscle, enabled respectively by its two main cellular constituents, the mature myofibers and satellite cells (SCs). Still, after 20 years of research, engineered muscle tissues fall short of mimicking contractile function and self-repair capacity of native skeletal muscle. To overcome this limitation, we set the thesis goals to: 1) generate a highly functional, self-regenerative engineered skeletal muscle and 2) explore mechanisms governing its formation and regeneration in vitro and survival and vascularization in vivo.

By studying myogenic progenitors isolated from neonatal rats, we first discovered advantages of using an adherent cell fraction for engineering of skeletal muscles with robust structure and function and the formation of a SC pool. Specifically, when synergized with dynamic culture conditions, the use of adherent cells yielded muscle constructs capable of replicating the contractile output of native neonatal muscle, generating >40 mN/mm2 of specific force. Moreover, tissue structure and cellular heterogeneity of engineered muscle constructs closely resembled those of native muscle, consisting of aligned, striated myofibers embedded in a matrix of basal lamina proteins and SCs that resided in native-like niches. Importantly, we identified rapid formation of myofibers early during engineered muscle culture as a critical condition leading to SC homing and conversion to a quiescent, non-proliferative state. The SCs retained natural regenerative capacity and activated, proliferated, and differentiated to rebuild damaged myofibers and recover contractile function within 10 days after the muscle was injured by cardiotoxin (CTX). The resulting regenerative response was directly dependent on the abundance of SCs in the engineered muscle that we varied by expanding starting cell population under different levels of basic fibroblast growth factor (bFGF), an inhibitor of myogenic differentiation. Using a dorsal skinfold window chamber model in nude mice, we further demonstrated that within 2 weeks after implantation, initially avascular engineered muscle underwent robust vascularization and perfusion and exhibited improved structure and contractile function beyond what was achievable in vitro.

To enhance translational value of our approach, we transitioned to use of adult rat myogenic cells, but found that despite similar function to that of neonatal constructs, adult-derived muscle lacked regenerative capacity. Using a novel platform for live monitoring of calcium transients during construct culture, we rapidly screened for potential enhancers of regeneration to establish that many known pro-regenerative soluble factors were ineffective in stimulating in vitro engineered muscle recovery from CTX injury. This led us to introduce bone marrow-derived macrophages (BMDMs), an established non-myogenic contributor to muscle repair, to the adult-derived constructs and to demonstrate remarkable recovery of force generation (>80%) and muscle mass (>70%) following CTX injury. Mechanistically, while similar patterns of early SC activation and proliferation upon injury were observed in engineered muscles with and without BMDMs, a significant decrease in injury-induced apoptosis occurred only in the presence of BMDMs. The importance of preventing apoptosis was further demonstrated by showing that application of caspase inhibitor (Q-VD-OPh) yielded myofiber regrowth and functional recovery post-injury. Gene expression analysis suggested muscle-secreted tumor necrosis factor-α (TNFα) as a potential inducer of apoptosis as common for muscle degeneration in diseases and aging in vivo. Finally, we showed that BMDM incorporation in engineered muscle enhanced its growth, angiogenesis, and function following implantation in the dorsal window chambers in nude mice.

In summary, this thesis describes novel strategies to engineer highly contractile and regenerative skeletal muscle tissues starting from neonatal or adult rat myogenic cells. We find that age-dependent differences of myogenic cells distinctly affect the self-repair capacity but not contractile function of engineered muscle. Adult, but not neonatal, myogenic progenitors appear to require co-culture with other cells, such as bone marrow-derived macrophages, to allow robust muscle regeneration in vitro and rapid vascularization in vivo. Regarding the established roles of immune system cells in the repair of various muscle and non-muscle tissues, we expect that our work will stimulate the future applications of immune cells as pro-regenerative or anti-inflammatory constituents of engineered tissue grafts. Furthermore, we expect that rodent studies in this thesis will inspire successful engineering of biomimetic human muscle tissues for use in regenerative therapy and drug discovery applications.

Droplet etching of deep nanoholes for filling with self-aligned complex quantum structures

Strain-free epitaxial quantum dots (QDs) are fabricated by a combination of Al local droplet etching (LDE) of nanoholes in AlGaAs surfaces and subsequent hole filling with GaAs. The whole process is performed in a conventional molecular beam epitaxy (MBE) chamber. Autocorrelation measurements establish single-photon emission from LDE QDs with a very small correlation function g (2)(0)≃ 0.01 of the exciton emission. Here, we focus on the influence of the initial hole depth on the QD optical properties with the goal to create deep holes suited for filling with more complex nanostructures like quantum dot molecules (QDM). The depth of droplet etched nanoholes is controlled by the droplet material coverage and the process temperature, where a higher coverage or temperature yields deeper holes. The requirements of high quantum dot uniformity and narrow luminescence linewidth, which are often found in applications, set limits to the process temperature. At high temperatures, the hole depths become inhomogeneous and the linewidth rapidly increases beyond 640 °C. With the present process technique, we identify an upper limit of 40-nm hole depth if the linewidth has to remain below 100 μeV. Furthermore, we study the exciton fine-structure splitting which is increased from 4.6 μeV in 15-nm-deep to 7.9 μeV in 35-nm-deep holes. As an example for the functionalization of deep nanoholes, self-aligned vertically stacked GaAs QD pairs are fabricated by filling of holes with 35 nm depth. Exciton peaks from stacked dots show linewidths below 100 μeV which is close to that from single QDs.

Formal function and phrase structure in contemporary music : Pierre Boulez’s late solo works and Sean Clarke’s "Lucretia Overture" and "4 Impromptus"

Cette thèse présente une théorie de la fonction formelle et de la structure des phrases dans la musique contemporaine, théorie qui peut être utilisée aussi bien comme outil analytique que pour créer de nouvelles œuvres. Deux concepts théoriques actuels aident à clarifier la structure des phrases : les projections temporelles de Christopher Hasty et la théorie des fonctions formelles de William Caplin, qui inclut le concept de l’organisation formelle soudée versus lâche (tight-knit vs. loose). Les projections temporelles sont perceptibles grâce à l’accent mis sur les paramètres secondaires, comme le style du jeu, l’articulation et le timbre. Des sections avec une organisation formelle soudée ont des projections temporelles claires, qui sont créées par la juxtaposition des motifs distincts, généralement sous la forme d'une idée de base en deux parties. Ces projections organisent la musique en phrases de présentation, en phrases de continuité et finalement, à des moments formels charnières, en phrases cadentielles. Les sections pourvues d’une organisation plus lâche tendent à présenter des projections et mouvements harmoniques moins clairs et moins d’uniformité motivique. La structure des phrases de trois pièces tardives pour instrument soliste de Pierre Boulez est analysée : Anthèmes I pour violon (1991-1992) et deux pièces pour piano, Incises (2001) et une page d’éphéméride (2005). Les idées proposées dans le présent document font suite à une analyse de ces œuvres et ont eu une forte influence sur mes propres compositions, en particulier Lucretia Overture pour orchestre et 4 Impromptus pour flûte, saxophone soprano et piano, qui sont également analysés en détail. Plusieurs techniques de composition supplémentaires peuvent être discernés dans ces deux œuvres, y compris l'utilisation de séquence mélodiques pour contrôler le rythme harmonique; des passages composés de plusieurs couches musicales chacun avec un structure de phrase distinct; et le relâchement de l'organisation formelle de matériels récurrents. Enfin, la composition de plusieurs autres travaux antérieurs a donné lieu à des techniques utilisées dans ces deux œuvres et ils sont brièvement abordés dans la section finale.