Behavior Of Granular Materials Under Cyclic And Repeated Loading

Thesis (Ph.D.) University of Alaska Fairbanks, 2003Granular layers are essential contributors to the structural integrity of the pavement system, their premature deformation radically decrease support of the asphalt concrete surface layer, thus leading to the early deterioration of the overall pavement structure. This research was conducted to better understand the behavior of granular materials when subjected to the complex nature of traffic loading. Long-term triaxial tests were conducted on typical Alaskan base course material using both repeated as well as cyclic loading to also account for the shear reversal effects induced by wheel load. Results show that the shear reversal component of the traffic loads, which have been ignored so far, induces considerable damage to the granular layers. Models were presented to predict the different soil moduli while also accounting the effect of strain hardening or densification due to the repetitive nature of the loads applied. Moreover, a simple yet powerful model was presented to predict accumulated permanent strains as function of the stress state, number of load repetitions and the strength level applied. The results obtained in this study also show a clear indication of the existence of given stress level limit beyond which incremental collapse of the system takes place. Furthermore, regions of instability of granular layers subjected to dynamic loading have been defined using a simple response parameter and monotonic shear strength of the soil. An effort was made to explain the instability zones identified in this research by the shakedown theory.* *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Microsoft Office

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Autoantibody detection for diagnosis in direct immunofluorescence negative mucous membrane pemphigoid: ocular and other sites compared

Objective: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. / Design: Prospective cross-sectional study. / Subjects and controls: 76 patients with MMP involving ocular and non-ocular sites with 45 matched controls. / Tests: Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies. / Main outcome measures: Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites. / Results: All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings. / Conclusions: Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available

Classical and Quantum Equations of Motion for a BTZ Black String in AdS Space

We investigate gravitational collapse of a $(3+1)$-dimensional BTZ black string in AdS space in the context of both classical and quantum mechanics. This is done by first deriving the conserved mass per unit length of the cylindrically symmetric domain wall, which is taken as the classical Hamiltonian of the black string. In the quantum mechanical context, we take primary interest in the behavior of the collapse near the horizon and near the origin (classical singularity) from the point of view of an infalling observer. In the absence of radiation, quantum effects near the horizon do not change the classical conclusions for an infalling observer, meaning that the horizon is not an obstacle for him/her. The most interesting quantum mechanical effect comes in when investigating near the origin. First, quantum effects are able to remove the classical singularity at the origin, since the wave function is non-singular at the origin. Second, the Schr\"odinger equation describing the behavior near the origin displays non-local effects, which depend on the energy density of the domain wall. This is manifest in that derivatives of the wavefunction at one point are related to the value of the wavefunction at some other distant point.Comment: 9 pages, 1 figure. Minor Clarification and corrections. Accepted for Publication in JHE

On Surface Plasmon Damping in Metallic Nanoparticles

Two possible mechanisms of surface plasmon (SP) oscillations damping in metallic nanoparticles (MNPs), not connected with electron-phonon interaction are investigated theoretically: a) the radiation damping of SP, b) resonant coupling of SP oscillations with electronic transitions in matrix. It is shown that the radiation damping rate is proportional to the number of electrons in MNP and therefore this channel of energy outflow from MNP becomes essential for relatively large particles. The investigation of second mechanism shows that the rate of SP oscillations energy leakage from MNP dos not depend on particle size and is fully determined by the optical characteristics of the matrix. It is demonstrated that for very small MNPs of 3-5 nm size, where the strong 3D size quantization effect suppresses the electron-phonon interaction, the resonance coupling in certain cases provides an effective energy outflow.Comment: 6 pages; E-mail address: [email protected]

NEWS AND NOTES 1994, VOL.4, NO.16

https://digitalcommons.rockefeller.edu/news_and_notes_1994/1002/thumbnail.jp

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Healthcare resource utilisation and mortality outcomes in international migrants to the UK: analysis protocol for a linked population-based cohort study using Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES) and the Office for National Statistics (ONS) [version 2; peer review: 1 approved with reservations, 1 not approved]

An estimated 14.2% (9.34 million people) of people living in the UK in 2019 were international migrants. Despite this, there are no large-scale national studies of their healthcare resource utilisation and little is known about how migrants access and use healthcare services. One ongoing study of migration health in the UK, the Million Migrants study, links electronic health records (EHRs) from hospital-based data, national death records and Public Health England migrant and refugee data. However, the Million Migrants study cannot provide a complete picture of migration health resource utilisation as it lacks data on migrants from Europe and utilisation of primary care for all international migrants. Our study seeks to address this limitation by using primary care EHR data linked to hospital-based EHRs and national death records.  Our study is split into a feasibility study and a main study. The feasibility study will assess the validity of a migration phenotype, a transparent reproducible algorithm using clinical terminology codes to determine migration status in Clinical Practice Research Datalink (CPRD), the largest UK primary care EHR. If the migration phenotype is found to be valid, the main study will involve using the phenotype in the linked dataset to describe primary care and hospital-based healthcare resource utilisation and mortality in migrants compared to non-migrants. All outcomes will be explored according to sub-conditions identified as research priorities through patient and public involvement, including preventable causes of inpatient admission, sexual and reproductive health conditions/interventions and mental health conditions. The results will generate evidence to inform policies that aim to improve migration health and universal health coverage

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference