Singular perturbation of quantum stochastic differential equations with coupling through an oscillator mode

Gough, John; Van Handel, R., (2007) 'Singular perturbation of quantum stochastic differential equations with coupling through an oscillator mode', Journal of Statistical Physics 127(3) pp.575-607 RAE2008

Vulnerability or resilience? Psycho-social factors associated with deliberate self-harm among adolescents

Background: Deliberate self-harm (DSH) is common among adolescents in Ireland and internationally. Psychological factors, negative life events and lifestyle factors have been found to be associated with self-harm in this group. However, large scale population-based studies of adolescent selfharm and its correlates have been lacking, and internationally a standardised methodology was needed to facilitate comparative studies. The focus on vulnerability which has been prevalent in this field has meant that research has failed to examine resilient adaptation among at-risk adolescents. Method: Data were obtained from a cross-sectional school-based study conducted in Ireland and in each of the six other centres which participated in the Child and Adolescent Self-harm in Europe (CASE) study. In Ireland, 3,881 adolescents in 39 schools in completing the anonymous questionnaire, while across all 7 centres, over 30,000 young people participated. Data were gathered on health and lifestyle, self-harm thoughts and behaviour, a wide range of life events, psychological characteristics (anxiety and depressive symptoms, self-esteem, impulsivity and coping style), and support available to young people. Results: This thesis reports the findings of the Irish CASE centre as well as one international study. The factors associated with DSH among Irish adolescents differed by gender, but among both genders drug use and knowing a friend who had engaged in self-harm were associated with DSH. Among Irish boys, strong associations were found between bullying and poor mental health and DSH. Among boys who had been bullied, psychological and school factors were associated with DSH, while family support was protective. Links between stressful life events, psychological characteristics and DSH within the international CASE sample were examined. Increased history of self-harm thoughts and acts was associated with greater depression, anxiety and impulsivity, lower self esteem and an increased prevalence of ten different negative life events, supporting the hypothesis of a “dose-response” relationship between these risk factors and the self-harm process. Associations between coping style, mental health factors (depressive symptoms, anxiety and self-esteem) and self-harm were examined among Irish adolescents. Emotion-oriented coping was strongly associated with poorer mental health and self-harm thoughts and acts. A mediating effect of emotion-oriented coping on associations between mental health factors and DSH was found for both genders and between problem-oriented coping and mental health factors for girls. Similar mediating effects of coping style were found when risk of self-harm thoughts was examined. Resilient adaptation among adolescents exposed to suicidal behaviour of others was examined. Self-harm thoughts were common in these adolescents. Among those exposed to suicidal behaviour of others, vulnerability factors were drug use and higher levels of anxiety among boys, while for girls drug use, bullying and abuse were vulnerability factors, while resilience was associated with higher self-esteem and use of problem-oriented coping. Conclusion: These findings can aid in the identification of young people at risk of self-harm in the school setting and highlight the importance of mental health, peer-related and lifestyle factors in the development of DSH. High-risk groups of young people such as bullying victims and those exposed to suicidal behaviour of others have distinctive profiles of risk factors which differ from those of their peers. Findings relating to the importance of positive coping skills can inform positive mental health programmes, many of which aim to enhance life skills and build resilience among young people. Knowledge of the factors associated with positive adaptation among at-risk adolescents can inform prevention efforts among this group.

Uniformly convergent finite element and finite difference methods for singularly perturbed ordinary differential equations

This thesis is concerned with uniformly convergent finite element and finite difference methods for numerically solving singularly perturbed two-point boundary value problems. We examine the following four problems: (i) high order problem of reaction-diffusion type; (ii) high order problem of convection-diffusion type; (iii) second order interior turning point problem; (iv) semilinear reaction-diffusion problem. Firstly, we consider high order problems of reaction-diffusion type and convection-diffusion type. Under suitable hypotheses, the coercivity of the associated bilinear forms is proved and representation results for the solutions of such problems are given. It is shown that, on an equidistant mesh, polynomial schemes cannot achieve a high order of convergence which is uniform in the perturbation parameter. Piecewise polynomial Galerkin finite element methods are then constructed on a Shishkin mesh. High order convergence results, which are uniform in the perturbation parameter, are obtained in various norms. Secondly, we investigate linear second order problems with interior turning points. Piecewise linear Galerkin finite element methods are generated on various piecewise equidistant meshes designed for such problems. These methods are shown to be convergent, uniformly in the singular perturbation parameter, in a weighted energy norm and the usual L2 norm. Finally, we deal with a semilinear reaction-diffusion problem. Asymptotic properties of solutions to this problem are discussed and analysed. Two simple finite difference schemes on Shishkin meshes are applied to the problem. They are proved to be uniformly convergent of second order and fourth order respectively. Existence and uniqueness of a solution to both schemes are investigated. Numerical results for the above methods are presented.

Uniformly convergent finite element methods for singularly perturbed parabolic partial differential equations

This thesis is concerned with uniformly convergent finite element methods for numerically solving singularly perturbed parabolic partial differential equations in one space variable. First, we use Petrov-Galerkin finite element methods to generate three schemes for such problems, each of these schemes uses exponentially fitted elements in space. Two of them are lumped and the other is non-lumped. On meshes which are either arbitrary or slightly restricted, we derive global energy norm and L2 norm error bounds, uniformly in the diffusion parameter. Under some reasonable global assumptions together with realistic local assumptions on the solution and its derivatives, we prove that these exponentially fitted schemes are locally uniformly convergent, with order one, in a discrete L∞norm both outside and inside the boundary layer. We next analyse a streamline diffusion scheme on a Shishkin mesh for a model singularly perturbed parabolic partial differential equation. The method with piecewise linear space-time elements is shown, under reasonable assumptions on the solution, to be convergent, independently of the diffusion parameter, with a pointwise accuracy of almost order 5/4 outside layers and almost order 3/4 inside the boundary layer. Numerical results for the above schemes are presented. Finally, we examine a cell vertex finite volume method which is applied to a model time-dependent convection-diffusion problem. Local errors away from all layers are obtained in the l2 seminorm by using techniques from finite element analysis.

Variations in total and differential milk somatic cell counts and plasmin levels and their role in proteolysis and quality of milk and cheese

Increased plasmin and plasminogen levels and elevated somatic cell counts (SCC) and polymorphonuclear leucocyte levels (PMN) were evident in late lactation milk. Compositional changes in these milks were associated with increased SCC. The quality of late lactation milks was related to nutritional status of herds, with milks from herds on a high plane of nutrition having composition and clotting properties similar to, or superior to, early-mid lactation milks. Nutritionally-deficient cows had elevated numbers of polymorphonuclear leucocytes (PMNs) in their milk, elevated plasmin levels and increased overall proteolytic activity. The dominant effect of plasmin on proteolysis in milks of low SCC was established. When present in elevated numbers, somatic cells and PMNs in particular had a more significant influence on the proteolysis of both raw and pasteurised milks than plasmin. PMN protease action on the caseins showed proteolysis products of two specific enzymes, cathepsin B and elastase, which were also shown in high SCC milk. Crude extracts of somatic cells had a high specificity on αs1-casein. Cheeses made from late lactation milks had increased breakdown of αs1-casein, suggestive of the action of somatic cell proteinases, which may be linked to textural defects in cheese. Late lactation cheeses also showed decreased production of small peptides and amino acids, the reason for which is unknown. Plasmin, which is elevated in activity in late lactation milk, accelerated the ripening of Gouda-type cheese, but was not associated with defects of texture or flavour. The retention of somatic cell enzymes in cheese curd was confirmed, and a potential role in production of bitter peptides identified. Cheeses made from milks containing high levels of PMNs had accelerated αs1-casein breakdown relative to cheeses made from low PMN milk of the same total SCC, consistent with the demonstrated action of PMN proteinases. The two types of cheese were determined significantly different by blind triangle testing.

Differential and numerical models of hysteretic systems with stochastic and deterministic inputs

Many deterministic models with hysteresis have been developed in the areas of economics, finance, terrestrial hydrology and biology. These models lack any stochastic element which can often have a strong effect in these areas. In this work stochastically driven closed loop systems with hysteresis type memory are studied. This type of system is presented as a possible stochastic counterpart to deterministic models in the areas of economics, finance, terrestrial hydrology and biology. Some price dynamics models are presented as a motivation for the development of this type of model. Numerical schemes for solving this class of stochastic differential equation are developed in order to examine the prototype models presented. As a means of further testing the developed numerical schemes, numerical examination is made of the behaviour near equilibrium of coupled ordinary differential equations where the time derivative of the Preisach operator is included in one of the equations. A model of two phenotype bacteria is also presented. This model is examined to explore memory effects and related hysteresis effects in the area of biology. The memory effects found in this model are similar to that found in the non-ideal relay. This non-ideal relay type behaviour is used to model a colony of bacteria with multiple switching thresholds. This model contains a Preisach type memory with a variable Preisach weight function. Shown numerically for this multi-threshold model is a pattern formation for the distribution of the phenotypes among the available thresholds.

Vulnerability and adaptation to climate change in Guam – a case-study of the perceptions, attitudes, behaviors, and knowledge of a small rural community towards their watershed

This thesis argues that examining the attitudes, perceptions, behaviors, and knowledge of a community towards their specific watershed can reveal their social vulnerability to climate change. Understanding and incorporating these elements of the human dimension in coastal zone management will lead to efficient and effective strategies that safeguard the natural resources for the benefit of the community. By having healthy natural resources, ecological and community resilience to climate change will increase, thus decreasing vulnerability. In the Pacific Ocean, climate and SLR are strongly modulated by the El Niño Southern Oscillation. SLR is three times the global average in the Western Pacific Ocean (Merrifield and Maltrud 2011; Merrifield 2011). Changes in annual rainfall in the Western North Pacific sub‐region from 1950-2010 show that islands in the east are getting much less than in the past, while the islands in the west are getting slightly more rainfall (Keener et al. 2013). For Guam, a small island owned by the United States and located in the Western Pacific Ocean, these factors mean that SLR is higher than any other place in the world and will most likely see increased precipitation. Knowing this, the social vulnerability may be examined. Thus, a case-study of the community residing in the Manell and Geus watersheds was conducted on the island of Guam. Measuring their perceptions, attitudes, knowledge, and behaviors should bring to light their vulnerability to climate change. In order to accomplish this, a household survey was administered from July through August 2010. Approximately 350 surveys were analysed using SPSS. To supplement this quantitative data, informal interviews were conducted with the elders of the community to glean traditional ecological knowledge about perceived climate change. A GIS analysis was conducted to understand the physical geography of the Manell and Geus watersheds. This information about the human dimension is valuable to CZM managers. It may be incorporated into strategic watershed plans, to better administer the natural resources within the coastal zone. The research conducted in this thesis is the basis of a recent watershed management plan for the Guam Coastal Management Program (see King 2014).

Differential inducibility of HLA class I and II antigens by r-IFN gamma in type III bare lymphocyte syndrome.

Case Reports

Measurement of the differential cross section for the reaction gamman-->pi- p from deuterium.

We report a measurement of the differential cross section for the gamman-->pi- p process from the CLAS detector at Jefferson Laboratory in Hall B for photon energies between 1.0 and 3.5 GeV and pion center-of-mass (c.m.) angles (thetac.m.) between 50 degrees and 115 degrees. We confirm a previous indication of a broad enhancement around a c.m. energy ([sqrt]s) of 2.1 GeV at thetac.m.=90 degrees in the scaled differential cross section s7dsigma/dt and a rapid falloff in a center-of-mass energy region of about 400 MeV following the enhancement. Our data show an angular dependence of this enhancement as the suggested scaling region is approached for thetac.m. from 70 degrees to 105 degrees.

Differential inhibition of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and TZM-bl cells by endotoxin-mediated chemokine and gamma interferon production.

Bacterial lipopolysaccharide (endotoxin) is a frequent contaminant of biological specimens and is also known to be a potent inducer of beta-chemokines and other soluble factors that inhibit HIV-1 infection in vitro. Though lipopolysaccharide (LPS) has been shown to stimulate the production of soluble HIV-1 inhibitors in cultures of monocyte-derived macrophages, the ability of LPS to induce similar inhibitors in other cell types is poorly characterized. Here we show that LPS exhibits potent anti-HIV activity in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) but has no detectable anti-HIV-1 activity in TZM-bl cells. The anti-HIV-1 activity of LPS in PBMCs was strongly associated with the production of beta-chemokines from CD14-positive monocytes. Culture supernatants from LPS-stimulated PBMCs exhibited potent anti-HIV-1 activity when added to TZM-bl cells but, in this case, the antiviral activity appeared to be related to IFN-gamma rather than to beta-chemokines. These observations indicate that LPS stimulates PBMCs to produce a complex array of soluble HIV-1 inhibitors, including beta-chemokines and IFN-gamma, that differentially inhibit HIV-1 depending on the target cell type. The results also highlight the need to use endotoxin-free specimens to avoid artifacts when assessing HIV-1-specific neutralizing antibodies in PBMC-based assays.

Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice.

Morphine induces antinociception by activating mu opioid receptors (muORs) in spinal and supraspinal regions of the CNS. (Beta)arrestin-2 (beta)arr2), a G-protein-coupled receptor-regulating protein, regulates the muOR in vivo. We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. To determine the general applicability of the (beta)arr2-muOR interaction in other neuronal systems, we have, in the present study, tested (beta)arr2 knock-out ((beta)arr2-KO) mice using the warm water tail-immersion paradigm, which primarily assesses spinal reflexes to painful thermal stimuli. In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Interestingly, however, after a delayed onset, they do ultimately develop morphine tolerance, although to a lesser degree than the wild-type (WT) controls. In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. These findings provide in vivo evidence that the muOR is differentially regulated in diverse regions of the CNS. Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent.

Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury.

Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of beta(2)AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because beta(2)ARs, unlike beta(1)ARs, couple to G(i) as well as G(s), we pretreated mice with the G(i) inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either betaARK1 (TGbetaARK1) or a betaARK1 inhibitor (TGbetaARKct). Recoveries of function, ATP, and phosphocreatine were higher in TGbetaARK1 hearts than in wild-type hearts. Despite basal contractility being elevated in TGbetaARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, beta(2)AR overexpression increased ischemic injury, whereas betaARK1 overexpression was protective. Ischemic injury in the beta(2)AR overexpressors was exacerbated by PTX treatment, implying that it was G(s) not G(i) activity that enhanced injury. Unlike beta(2)AR overexpression, basal contractility was increased by betaARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.

An approach to the study of G-protein-coupled receptor kinases: an in vitro-purified membrane assay reveals differential receptor specificity and regulation by G beta gamma subunits.

Phosphorylation of GTP-binding-regulatory (G)-protein-coupled receptors by specific G-protein-coupled receptor kinases (GRKs) is a major mechanism responsible for agonist-mediated desensitization of signal transduction processes. However, to date, studies of the specificity of these enzymes have been hampered by the difficulty of preparing the purified and reconstituted receptor preparations required as substrates. Here we describe an approach that obviates this problem by utilizing highly purified membrane preparations from Sf9 and 293 cells overexpressing G-protein-coupled receptors. We use this technique to demonstrate specificity of several GRKs with respect to both receptor substrates and the enhancing effects of G-protein beta gamma subunits on phosphorylation. Enriched membrane preparations of the beta 2- and alpha 2-C2-adrenergic receptors (ARs, where alpha 2-C2-AR refers to the AR whose gene is located on human chromosome 2) prepared by sucrose density gradient centrifugation from Sf9 or 293 cells contain the receptor at 100-300 pmol/mg of protein and serve as efficient substrates for agonist-dependent phosphorylation by beta-AR kinase 1 (GRK2), beta-AR kinase 2 (GRK3), or GRK5. Stoichiometries of agonist-mediated phosphorylation of the receptors by GRK2 (beta-AR kinase 1), in the absence and presence of G beta gamma, are 1 and 3 mol/mol, respectively. The rate of phosphorylation of the membrane receptors is 3 times faster than that of purified and reconstituted receptors. While phosphorylation of the beta 2-AR by GRK2, -3, and -5 is similar, the activity of GRK2 and -3 is enhanced by G beta gamma whereas that of GRK5 is not. In contrast, whereas GRK2 and -3 efficiently phosphorylate alpha 2-C2-AR, GRK5 is quite weak. The availability of a simple direct phosphorylation assay applicable to any cloned G-protein-coupled receptor should greatly facilitate elucidation of the mechanisms of regulation of these receptors by the expanding family of GRKs.

Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues.

Brain tumors are typically resistant to conventional chemotherapeutics, most of which initiate apoptosis upstream of mitochondrial cytochrome c release. In this study, we demonstrate that directly activating apoptosis downstream of the mitochondria, with cytosolic cytochrome c, kills brain tumor cells but not normal brain tissue. Specifically, cytosolic cytochrome c is sufficient to induce apoptosis in glioblastoma and medulloblastoma cell lines. In contrast, primary neurons from the cerebellum and cortex are remarkably resistant to cytosolic cytochrome c. Importantly, tumor tissue from mouse models of both high-grade astrocytoma and medulloblastoma display hypersensitivity to cytochrome c when compared with surrounding brain tissue. This differential sensitivity to cytochrome c is attributed to high Apaf-1 levels in the tumor tissue compared with low Apaf-1 levels in the adjacent brain tissue. These differences in Apaf-1 abundance correlate with differences in the levels of E2F1, a previously identified activator of Apaf-1 transcription. ChIP assays reveal that E2F1 binds the Apaf-1 promoter specifically in tumor tissue, suggesting that E2F1 contributes to the expression of Apaf-1 in brain tumors. Together, these results demonstrate an unexpected sensitivity of brain tumors to postmitochondrial induction of apoptosis. Moreover, they raise the possibility that this phenomenon could be exploited therapeutically to selectively kill brain cancer cells while sparing the surrounding brain parenchyma.

Community Vulnerability to Malaria in Madre de Dios, Peru

Construction of a highway and artisanal gold mining have contributed to population and land use changes within the department of Madre de Dios, Peru. Such changes are expected to alter malaria rates due to impacts on vector habitat and human exposure. Vulnerability, as defined by the possibility of bereavement of a physical good or abstract state, is useful for understanding which communities are most likely to be adversely impacted by hazards such as malaria. A model defining susceptibility (SUS) and lack of resilience (LOR) was used to create an index of vulnerability to malaria for 40 communities in Madre de Dios. Indicators of SUS and LOR were developed from household and community data and combined into a final vulnerability index score. Vulnerability scores ranged between 0.13 and 0.31 with a mean of 0.21. Communities were grouped according to standard deviations from the mean. The most vulnerable communities (>1.5 standard deviations from mean) were located in the southern portion of the study area. When the dimension scores were compared for all communities, scores were generally higher in the susceptibility dimension than in the lack of resilience dimension. Examination of the indicator scores of individual communities revealed that drivers of vulnerability vary across the department. Therefore, targeted interventions addressing specific aspects of vulnerability may be useful. Finally, a predicted vulnerability surface was created for a 10 km buffer surrounding the Interoceanic Highway in Madre de Dios.