Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.

Structural Polymorphism of the Nucleosomal DNA and Implications for Protein Binding

A nucleosome forms a basic unit of the chromosome structure. A biologically relevant question is how much of the nucleosomal conformational space is accessible to protein-free DNA, and what proportion of the nucleosomal conformations are induced by bound histones. To investigate this, we have analysed high resolution xray crystal structure datasets of DNA in protein-free as well as protein-bound forms, and compared the dinucleotide step parameters for the two datasets with those for high resolution nucleosome structures. Our analysis shows that most of the dinucleotide step parameter values for the nucleosome structures lie within the range accessible to protein-free DNA, indirectly indicating that the histone core plays more of a stabilizing role. The nucleosome structures are observed to assume smooth and nearly planar curvature, implying that ‘normal’ B-DNA like parameters can give rise to a curved geometry at the gross structural level. Different nucleosome

Spatial model of site index based on Y-ray spectrometry and a digital elevation model for two Pinus species in Tuan Toolara State Forest, Queensland, Australia

Site index prediction models are an important aid for forest management and planning activities. This paper introduces a multiple regression model for spatially mapping and comparing site indices for two Pinus species (Pinus elliottii Engelm. and Queensland hybrid, a P. elliottii x Pinus caribaea Morelet hybrid) based on independent variables derived from two major sources: g-ray spectrometry (potassium (K), thorium (Th), and uranium (U)) and a digital elevation model (elevation, slope, curvature, hillshade, flow accumulation, and distance to streams). In addition, interpolated rainfall was tested. Species were coded as a dichotomous dummy variable; interaction effects between species and the g-ray spectrometric and geomorphologic variables were considered. The model explained up to 60% of the variance of site index and the standard error of estimate was 1.9 m. Uranium, elevation, distance to streams, thorium, and flow accumulation significantly correlate to the spatial variation of the site index of both species, and hillshade, curvature, elevation and slope accounted for the extra variability of one species over the other. The predicted site indices varied between 20.0 and 27.3 m for P. elliottii, and between 23.1 and 33.1 m for Queensland hybrid; the advantage of Queensland hybrid over P. elliottii ranged from 1.8 to 6.8 m, with the mean at 4.0 m. This compartment-based prediction and comparison study provides not only an overview of forest productivity of the whole plantation area studied but also a management tool at compartment scale.

Spinaalistenoosipotilaiden psyykkinen hyvinvointi ennen leikkaushoitoa ja sen jälkeen

Surgical treatment of lumbar spinal stenosis (LSS) is a treatment option for those patients who remain severely symptomatic after a course of conservative treatment. Majority of the patients treated surgically enjoy good-to-excellent outcomes with respect to pain alleviation and functional recovery. However, between 20% and 40% of the patients who have surgery for LSS do not benefit from it. The knowledge of the psychological factors associated with recovery and treatment outcome is still scarce. The aim of this study was to assess LSS patients selected for surgical treatment. Specifically, the study assessed the prevalence of depression (Beck Depression Inventory, BDI) before surgical treatment and three months after the treatment. Also preoperative life satisfaction (four-item Life Satisfaction scale) of the LSS patients was studied. Furthermore, the patients satisfaction with surgery outcome at the three months postoperative stage was studied. One-fifth (20%) of the LSS-patients were found to have depression preoperatively. The patients assessments of the pain intensity or location were not associated with depression. The factors that did associate with depression were subjective disability of everyday living and poor life satisfaction. In addition to this, low sense of coherence and poor life satisfaction were associated with depression in logistic regression models. Significant associations were seen between preoperative depression and postoperative high disability scores, high symptom severity scores and higher pain intensity ratings. The patients with continuous depression (60% of the patients who had preoperative depression) showed less improvement in symptom severity, disability, pain and walking capacity than the patients who did not experience depression at any stage. In those patients who recovered from depression (35% of the patients with preoperative depression), the postoperative improvement was rather similar to the improvement seen in the normal mood group. One-fourth (25%) of the preoperative patients with LSS were found to be dissatisfied with life. The dissatisfied patients were significantly younger and had more self-reported somatic comorbidity. The dissatisfied patients had also elevated subjective disability scores and more extensive pain locations. Also lower coping resources and higher BDI scores were associated with life dissatisfaction. Younger age and somatic comorbidity were associated with life dissatisfaction in regression models. Two-thirds (66%) of the patients were at least clearly satisfied with the surgery outcome at three months postoperative stage. In group comparisons, the lack of physical, functional and emotional well-being was associated with the patients dissatisfaction with the surgery outcome. Younger age, postoperative symptom severity, disability and depression were independently associated with dissatisfaction with the surgery outcome. The results show that depression and psychological well-being are important factors with respect to LSS patients functional ability and recovery both before and three months after surgical treatment. Therefore, the clinical practice recommendations should include an assessment of depression

Use of part records in Merino breeding programs - The inheritance of wool growth and fibre traits during different times of the year to determine their value in Merino breeding programs

Fibre diameter can vary dramatically along a wool staple, especially in the Mediterranean environment of southern Australia with its dry summers and abundance of green feed in spring. Other research results have shown a very low phenotypic correlation between fibre diameter grown between seasons. Many breeders use short staples to measure fibre diameter for breeding purposes and also to promote animals for sale. The effectiveness of this practice is determined by the relative response to selection by measuring fibre traits on a full 12 months wool staple as compared to measuring them only on part of a staple. If a high genetic correlation exists between the part record and the full record, then using part records may be acceptable to identify genetically superior animals. No information is available on the effectiveness of part records. This paper investigated whether wool growth and fibre diameter traits of Merino wool grown at different times of the year in a Mediterranean environment, are genetically the same trait, respectively. The work was carried out on about 7 dyebanded wool sections/animal.year, on ewes from weaning to hogget age, in the Katanning Merino resource flocks over 6 years. Relative clean wool growth of the different sections had very low heritability estimates of less than 0.10, and they were phenotypically and genetically poorly correlated with 6 or 12 months wool growth. This indicates that part record measurement of clean wool growth of these sections will be ineffective as indirect selection criteria to improve wool growth genetically. Staple length growth as measured by the length between dyebands, would be more effective with heritability estimates of between 0.20 and 0.30. However, these measurements were shown to have a low genetic correlation with wool grown for 12 months which implies that these staple length measurements would only be half as efficient as the wool weight for 6 or 12 months to improve total clean wool weight. Heritability estimates of fibre diameter, coefficient of variation of fibre diameter and fibre curvature were relatively high and were genetically and phenotypically highly correlated across sections. High positive phenotypic and genetic correlations were also found between fibre diameter, coefficient of variation of fibre diameter and fibre curvature of the different sections and similar measurements for wool grown over 6 or 12 months. Coefficient of variation of fibre diameter of the sections also had a moderate negative phenotypic and genetic correlation with staple strength of wool staples grown over 6 months indicating that coefficient of variation of fibre diameter of any section would be as good an indirect selection criterion to improve stable strength as coefficient of variation of fibre diameter for wool grown over 6 or 12 months. The results indicate that fibre diameter, coefficient of variation of fibre diameter and fibre curvature of wool grown over short periods of time have virtually the same heritability as that of wool grown over 12 months, and that the genetic correlation between fibre diameter, coefficient of variation of fibre diameter and fibre curvature on part and on full records is very high (rg > 0.85). This indicates that fibre diameter, coefficient of variation of fibre diameter and fibre curvature on part records can be used as selection criteria to improve these traits. However, part records of greasy and clean wool growth would be much less efficient than fleece weight for wool grown over 6 or 12 months because of the low heritability of part records and the low genetic correlation between these traits on part records and on wool grown for 12 months.

Australian Bat Lyssavirus

In Chapter 1, the literature relating to rabies virus and the rabies like lyssaviruses is reviewed. In Chapter 2, data are presented from 1170 diagnostic submissions for ABLV testing by fluorescent antibody test (Centocor FAT). All 27 non-bat submissions were ABLV-negative. Of 1143 bat accessions 74 (16%) were ABLV-positive, including 69 of 974 (7.1%) flying foxes (Pteropus spp.), 5 of 7 (71.4%) Saccolaimus flaviventris (Yellow-bellied sheathtail bats), none of 151 other microchiropteran bats, and none of 11 unidentified bats. Statistical analysis of data from 868 wild Black, Grey-headed, Little Red and Spectacled flying foxes (Pteropus alecto, P. poliocephalus, P. scapulatus, and P. conspicillatus) indicated that three factors; species, health status and age were associated with significant (p< 0.001) differences in the proportion of ABLV-positive bats. Other factors including sex, whether the bat bit a person or animal, region, year, and season submitted, were not associated with ABLV. Case data for 74 ABLV-positive bats, including the circumstances in which they were found and clinical signs, is presented. In Chapter 3, the aetiological diagnosis was investigated for 100 consecutive flying fox submissions with neurological signs. ABLV (32%), spinal and head injuries (29%), and neuro-angiostrongylosis (18%) accounted for most neurological syndromes in flying foxes. No evidence of lead poisoning was found in unwell (n=16) or healthy flying foxes (n=50). No diagnosis was reached for 16 cases, all of which were negative for ABLV by TaqMan PCR. The molecular diversity of ABLV was examined in Chapter 4 by sequencing 36 bases of the leader sequence, the entire N gene, and start of the P gene of 28 isolates from pteropid bats and 3 isolates from Yellow-bellied sheathtail (YBST) bats. Phylogenetic analysis indicated all ABLV isolates clustered together as a discrete group within the Lyssavirus genera closely related to rabies virus and European bat lyssavirus-2 isolates. The ABLV lineage consisted of two variants; one (ybst-ABLV) consisted of isolates only from YBST bats, the other (pteropid-ABLV) was common to Black, Grey-headed and Little Red flying foxes. No associations were found between the sequences and either the geographical location or year found, or individual flying fox species. In Chapter 5, 15 inocula prepared from the brains or salivary glands of naturally-infected bats were evaluated by intracerebral (IC) and footpad (FP) inoculation of Quackenbush mice in order to select and characterize a highly virulent inoculum for further use in bats (Inoculum 5). In Chapter 6, nine Grey-headed flying foxes were inoculated with 105.2 to 105.5 MICED50 of Inoculum 5 divided into four sites, left footpad, pectoral muscle, temporal muscle and muzzle. Another bat was inoculated with half this dose divided into the footpad and pectoral muscle only. Seven of 10 bats developed clinical disease of 1 to 4 days duration between PI-days 10 and 19 and were shown to be ABL-positive by FAT, HAM immunoperoxidase staining, virus isolation in mice, and TaqMan PCR. Five of the seven bats displayed overt aggression, one died during a seizure, and one showed intractable agitation, pacing, tremors, and ataxia. Viral antigen was demonstrated throughout the central and peripheral nervous systems and in the epithelial cells of the submandibular salivary glands (n=4). All affected bats had mild to moderate non-suppurative meningoencephalitis and severe ganglioneuritis. No ABLV was detected in three bats that remained well until the end of the experiment on day 82. One survivor developed a strong but transient antibody response. In Chapter 7, the relative virulence of inocula prepared from the brains and salivary glands of experimentally infected flying foxes was evaluated in mice by IC and FP inoculation and TaqMan assay. The effects in mice were correlated to the TaqMan CT value and indicated a crude association between virulence and CT value that has potential application in the selection of inocula. In Chapter 8, 36 Black and Grey-headed flying foxes were vaccinated with one (day 0) or two (+ day 28) doses of Nobivac rabies vaccine and co-vaccinated with keyhole limpet haemocyanin (KLH). All bats responded to the Nobivac vaccine with a rabies-RFFIT titer > 0.5 IU/mL that is nominally indicative of protective immunity. Plasma from bats with rabies titres >2 IU/mL had cross-neutralising ABLV titres >1:154. A specifically developed ELISA detected a strong but transient response to KLH.

Hypoxic corneal changes following 8 hours of scleral contact lens wear

- Purpose To examine the change in corneal thickness and posterior curvature following 8 hours of miniscleral contact lens wear. - Methods Scheimpflug imaging (Pentacam HR, Oculus) was captured before, and immediately following, 8 hours of miniscleral contact lens wear for 15 young (mean age 22 ± 3 years), healthy participants with normal corneae. Natural diurnal variations were considered by measuring baseline corneal changes obtained on a separate control day without contact lens wear. - Results Over the central 6 mm of the cornea, a small, but highly statistically significant amount of edema was observed following 8 hours of miniscleral lens wear, after accounting for normal diurnal fluctuations (mean ± standard deviation percentage swelling 1.70 ± 0.98%, p < 0.0001). Posterior corneal topography remained stable following lens wear (-0.01 ± 0.07 mm steepening over the central 6 mm, p = 0.60). The magnitude of posterior corneal topographical changes following lens wear did not correlate with the extent of lens-related corneal edema (r = -0.16, p = 0.57). Similarly, the initial central corneal vault (maximum post-lens tear layer depth) was not associated with corneal swelling following lens removal (r = 0.27, p = 0.33). - Conclusions While a small amount of corneal swelling was induced following 8 hours of miniscleral lens wear (on average <2%), modern high Dk miniscleral contact lenses that vault the cornea do not induce clinically significant corneal edema or hypoxic related posterior corneal curvature changes during short-term wear. Longer-term studies of compromised eyes (e.g. corneal ectasia) are still required to inform the optimum lens and fitting characteristics for safe scleral lens wear to minimize corneal hypoxia.

Myelodysplasia as a cause of hindlimb ataxia in two beef calves.

Myelodysplasia is a general term referring to abnormal development of the spinal cord. Unless associated with vertebral malformations, it can be difficult to distinguish clinically from other causes of spinal cord disease. These case reports describe the clinical and pathological findings in two calves with a distinctive non-progressive pelvic limb ataxia. The syndrome was observed in two calves on a large, extensively managed beef cattle property near Richmond, north Queensland. Both calves had similar clinical signs, including hindlimb ataxia with swaying of the pelvis and a well-coordinated bilateral hopping-like action. The differential diagnoses are discussed. A focal or diffuse myelodysplasia should be suspected in calves that have exhibited a non-progressive hindlimb ataxia from birth.

Cholesterol-Esterifying Enzymes in Developing Rat Brain

A cholesterol-esterifying enzyme which incorporates exogenous fatty acids into cholesterol esters in the presence of ATP and coenzyme A was demonstrated in 15-day-old rat brain. This enzyme was maximally active at pH 7.4 and distinct from the cholesterol-esterifying enzyme reported earlier (Eto and Suzuki, 1971), which has a pH optimum at 5.2 and does not require cofactors. Properties of the two enzymes have been compared. Both the enzymes showed negligible esterification with acetate and were maximally active with oleic acid. The pH 5.2 enzyme esterified desmosterol, lanosterol and cholesterol at about the same rate, while the pH 7.4 enzyme was only 50% as active ith lanosterol as it was with cholesterol and desmosterol. Phosphatidyl serine stimulated the pH 5.2 enzyme but not the pH 7.4 enzyme. Phosphatidyl choline and sodium taurocholate showed no effect on either of the enzymes. Both the enzymes were associated with particulate fractions, but the pH 7.4 enzyme was localized more in the microsomes. Purified myelin showed 2.6-fold and 1.5-fold higher specific activities of pH 5.2 and 7.4 enzymes respectively, when compared with homogenate. About 7-10% of total activity of both the enzymes was associated with purified myelin. Brain stem and spinal cord showed higher specific activity of pH 5.2 enzyme than cerebral cortex and cerebellum, while pH 7.4 enzyme specific activity was higher in cerebellum and brain stem than in cerebral cortex and spinal cord. Microsomal pH 7.4 activity showed progressive increase prior to the active period of myelination, reaching a maximum on the 15th day after birth and declined to 20% of the peak activity by 30 days. In contrast, pH 5.2 enzyme reached maximum activity about the 6th day after birth and remained at this level well into adulthood. In 15-day-old rat brain, pH 7.4 enzyme had five to six times higher specific activity than pH 5.2 enzyme, while in adults the activities were equal. The pH 7.4 enzyme showed a threefold higher specific activity than pH 5.2 enzyme in myelin from 15-day-old rats, but in adults the reverse was true. Key Words: Cholesterol esterifying enzymes-Developing rat brain-Myelination. Jagannatha H. M. and Sastry P. S. Cholesterol-esterifying enzymes in developing rat brain. J. Neurochem. 36, 1352- 1360 (1981).

Continuation of limit cycles near saddle homoclinic points using splines in phase space

We present a new algorithm for continuation of limit cycles of autonomous systems as a system parameter is varied. The algorithm works in phase space with an ordered set of points on the limit cycle, along with spline interpolation. Currently popular algorithms in bifurcation analysis packages compute time-domain approximations of limit cycles using either shooting or collocation. The present approach seems useful for continuation near saddle homoclinic points, where it encounters a corner while time-domain methods essentially encounter a discontinuity (a relatively short period of rapid variation). Other phase space-based algorithms use rescaled arclength in place of time, but subsequently resemble the time-domain methods. Compared to these, we introduce additional freedom through a variable stretching of arclength based on local curvature, through the use of an auxiliary index-based variable. Several numerical examples are presented. Comparisons with results from the popular package, MATCONT, are favorable close to saddle homoclinic points.

Experimental and computational studies on lipoprotein lipolysis at acidic pH

Atherosclerosis is a disease of the arteries; its characteristic features include chronic inflammation, extra- and intracellular lipid accumulation, extracellular matrix remodeling, and an increase in extracellular matrix volume. The underlying mechanisms in the pathogenesis of advanced atherosclerotic plaques, that involve local acidity of the extracellular fluid, are still incompletely understood. In this thesis project, my co-workers and I studied the different mechanisms by which local extracellular acidity could promote accumulation of the atherogenic apolipoprotein B-100 (apoB-100)-containing plasma lipoprotein particles in the inner layer of the arterial wall, the intima. We found that lipolysis of atherogenic apoB-100-containing plasma lipoprotein particles (LDL, IDL, and sVLDL) by the secretory phospholipase A2 group V (sPLA2-V) enzyme, was increased at acidic pH. Also, the binding of apoB-100-containing plasma lipoprotein particles to human aortic proteoglycans was dramatically enhanced at acidic pH. Additionally, lipolysis by sPLA2-V enzyme further increased this binding. Using proteoglycan-affinity chromatography, we found that sVLDL lipoprotein particles consist of populations, differing in their affinities toward proteoglycans. These populations also contained different amounts of apolipoprotein E (apoE) and apolipoprotein C-III (apoC-III); the amounts of apoC-III and apoE per particle were highest in the population with the lowest affinity toward proteoglycans. Since PLA2-modification of LDL particles has been shown to change their aggregation behavior, we also studied the effect of acidic pH on the monolayer structure covering lipoprotein particles after PLA2-induced hydrolysis. Using molecular dynamics simulations, we found that, in acidity, the monolayer is more tightly packed laterally; moreover, its spontaneous curvature is negative, suggesting that acidity may promote lipoprotein particles fusion. In addition to extracellular lipid accumulation, the apoB-100-containing plasma lipoprotein particles can be taken up by inflammatory cells, namely macrophages. Using radiolabeled lipoprotein particles and cell cultures, we showed that sPLA2-V-modification of LDL, IDL, and sVLDL lipoproteins particles, at neutral or acidic pH, increased their uptake by human monocyte-derived macrophages.

Motion of a viscous fluid with suspended particles in a curved tube

In this paper we have discussed the motion of a viscous fluid with suspended particles through a curved tube of small curvature ratio. The system is treated as two separate interacting continua. Solutions for axial and secondary velocities are obtained in the form of asymptotic expansions in powers of Dean Number. The streamline pattern for the particulate phase reveals many interesting features. The influence of the particulate continium on the fluid is described by the parameter τ which depends on the density ratio of the two continua. The concentration distribution of the particles in a given cross section is determined. It is noticed that the particles move closer to the wall for certain values of the concentration and the density ratio.

The Pharmacology of Oxycodone : Studies In Vitro, In Vivo and In Humans

The antinociceptive properties of oxycodone and its metabolites were studied in models of thermal and mechanical nociception and in the spinal nerve ligation (SNL) model of neuropathic pain in rats. Oxycodone induced potent antinociception after subcutaneous (s.c.) administration in all models of nociception used in rats compared with morphine, methadone and its enantiomers. In the SNL model of neuropathic pain in rats, oxycodone produced dose dependent antinociception after s.c. administration. The antinociceptive effects of s.c. oxycodone were antagonized by naloxone but not by nor-binaltorphimine (Nor-BNI) a selective κ-opioid receptor antagonist indicating that the antinociceptive properties of oxycodone are predominantly μ-opioid receptor-mediated. The antinociceptive activity of oxymorphone, noroxycodone, and noroxymorphone, oxidative metabolites of oxycodone, were studied to determine their role in the oxycodone-induced antinociception in the rat. Of the metabolites of oxycodone s.c. administration of oxymorphone produced potent thermal and mechanical antinociception. Noroxycodone had a poor antinociceptive effect and noroxymorphone was inactive. Oxycodone produced naloxone-reversible antinociception after intrathecal (i.t) administration with a poor potency compared with morphine and oxymorphone. This seems to be related to the low efficacy and potency of oxycodone to stimulate μ-opioid receptor activation in the spinal cord in μ-opioid receptor agonist-stimulated (GTP)γ[S] autoradiography, compared with morphine and oxymorphone. All metabolites studied were more potent than oxycodone after i.t. administration. I.t. noroxymorphone induced a significantly longer lasting antinociceptive effect compared with the other drugs studied. The role of cytochrome P450 (CYP) 2D6-mediated metabolites on the analgesic activity of oxycodone in humans was studied by blocking the CYP2D6-mediated metabolism of oxycodone with paroxetine. Paroxetine co-administration had no effect on the analgesic effect of oxycodone compared with placebo in chronic pain patients, indicating that oxycodone-induced analgesia and adverse-effects are not dependent of the CYP2D6-mediated metabolism in humans. Although oxycodone has many pharmacologically active metabolites, they seem to have an insignificant role in oxycodone-induced antinociception in humans and rats.

Stresses around two equal circular elastic inclusions in a pressurised cylindrical shell

The stress problem of two equal circular elastic inclusions in a pressurised cylindrical shell has been solved by using single inclusion solutions together with Graf’s addition theorem. The effect of the inter-inclusion distance on the interface stresses in the shell as well as in the inclusion is studied. The results obtained for small values of curvature parameter fi @*=(a*/8Rt) [12(1-v*)]“*, a, R, t being inclusion radius and shell radius and thickness) when compared with the flat-plate results show good agreement. The results obtained in non-dimensional form are presented graphically.

An elementary approach to gap theorems

Using elementary comparison geometry, we prove: Let (M, g) be a simply-connected complete Riemannian manifold of dimension >= 3. Suppose that the sectional curvature K satisfies -1-s(r) <= K <= -1, where r denotes distance to a fixed point in M. If lim(r ->infinity) e(2r) s(r) = 0, then (M, g) has to be isometric to H-n.The same proof also yields that if K satisfies -s(r) <= K <= 0 where lim(r ->infinity) r(2) s(r) = 0, then (M, g) is isometric to R-n, a result due to Greene and Wu.Our second result is a local one: Let (M, g) be any Riemannian manifold. For a E R, if K < a on a geodesic ball Bp (R) in M and K = a on partial derivative B-p (R), then K = a on B-p (R).