Many studies have attempted to detect structural damage by examining differences in the frequency response functions of a structure before and after damage. In an experimental setting, this variation can not be attributed solely to the addition of damage. Other sources of variation include testing and structure variation. Examples of testing variation include the error introduced by modal parameter extraction, measurement noise, and the mass loading of the accelerometer. Structure variability is due to slight differences in the supposedly identical structures. Dimensional tolerancing is one example. This study began with six "identical" undamaged aluminum cylinders, of which three were later damaged to varying extents. The frequency response functions of the undamaged and damaged cylinders were measured. Also, the frequency response function of the same undamaged cylinder was measured multiple times to investigate testing variation. The contributions of testing, cylinder, and damage variation to the differences between cylinder responses was elucidated by specifically examining their frequency response functions in two ways: comparing the natural frequencies and directly investigating the entire frequency response function. The curvature of the frequency response functions was then used to determined the presence, location, and severity of the imparted damage. / Master of Science

Yes / Engineered Cementitious Composites (ECC) is a material which possesses advanced self-healing properties. Although the self-healing performance of ECC has been revealed in numerous studies, only small-scale, laboratory-size specimens have been used to assess it under fixed laboratory conditions and curing techniques. In order to evaluate the effect of intrinsic self-healing ability of ECC on the properties of structural-size, large-scale reinforced-beam members, specimens with four different shear span to effective depth (a/d) ratios, ranging from 1 to 4, were prepared to evaluate the effects of shear and flexural deformation. To ensure a realistic assessment, beams were cured using wet burlap, similar to on-site curing. Each beam was tested for mechanical properties including load-carrying capacity, deflection capacity, ductility ratio, yield stiffness, energy absorption capacity, and the influence of self-healing, by comparing types of failure and cracking. Self-healed test beams showed higher strength, energy absorption capacity and ductility ratio than damaged test beams. In test beams with an a/d ratio of 4 in which flexural behavior was prominent, self-healing application was highly successful; the strength, energy absorption capacity and ductility ratios of these beams achieved the level of undamaged beams. In addition, flexural cracks healed better, helping recover the properties of beams with predominantly flexural cracks rather than shear cracks. / The authors gratefully acknowledge the financial assistance of the Scientific and Technical Research Council (TUBITAK) of Turkey provided under Project: MAG-112M876 and the Turkish Academy of Sciences, Young Scientist Award program. The second author would also like to acknowledge the financial support of TÜBITAK for the 2219 Scholarship.

Linear genomes end in characteristic structures consisting of repetitive DNA and proteins: the telomeres. These play two critical roles: on one hand they avoid the of loss of genetic information due to the incomplete replication of the chromosome ends and on the other, they provide capping structures for chromosome termini, differentiating them from double strand breaks. Telomeres contain specialized proteins (the shelterin complex), as well as proteins present elsewhere on the chromosomes (chromatin remodelling, DNA damage repair and response factors). Interestingly, several DNA damage factors are required for proper telomere maintenance, drawing a thin line between telomere protection and their recognition as broken DNA ends. Loss of telomere integrity has severe consequences for the cell, namely it can induce replicative senescence and cellular aging, or it can contribute to tumorigenesis. How telomeres are capped and how they are perceived by the cell when they become dysfunctional is essential for our understanding of the contribution of loss of telomere integrity to aging and disease. In order to unravel new factors involved in telomere maintenance, siRNA screens were performed. The optimization process has confirmed both telomeric foci and telomere dysfunction-induced foci (TIFs) as suitable readouts and the screens performed generated a list of potential candidate genes involved in telomere biology. Although some of the candidate genes tested in this work failed the validation process, other genes deserve further analysis. In addition this work also studied the role of several DNA damage factors at uncapped telomeres. Furthermore, BRCA1, CtIP and EXO1 were found to be critical for the formation of end-to-end fusions generated after TRF2 inactivation. The requirement of this proteins in this process, suggests that not only that not only the classical non-homologous end joining (C-NHEJ) pathway is active at TRF2-depelted telomeres, but emphasises the multiplicity of mechanisms that act to repair dysfunctional telomeres.

The DNA damage response (DDR) is a complex signalling cascade triggered in response to stress, in an attempt to maintain genomic integrity. Components of this pathway, such as ATM-mediated signalling, have been proposed to act as a barrier in the early stages of tumourigenesis. Regions of low oxygen concentrations (hypoxia) occur in most solid tumours and are associated with a poor prognostic outcome. Here, we investigated the DDR induced following hypoxia-induced replication stress in an attempt to decipher the mechanism of ATM activation in response to physiological stresses that do not induce DNA damage. We hypothesized that hypoxia-mediated chromatin changes could impact on ATM signalling. We have characterised H3 methylation in response to hypoxia and found oxygen dependent changes in H3K9me3, including both global and replication fork associated increases in this histone modification. Importantly, we have found that decreases in H3K9me3 result in loss or attenuation of ATM activation. Notably, in a background of replication stress and increased H3K9me3, ATM inhibition or loss leads to accumulation of DNA damage and a significant decrease in replication rates in hypoxia. We propose that when replication stress occurs in the presence of hypoxia-induced chromatin changes, ATM activation is facilitated by the induction of H3K9me3. In this context, we propose a novel and stress specific role for ATM-mediated signalling in maintaining replication and preventing the generation of DNA breaks that may compromise genomic integrity. Moreover, the biological consequences of the hypoxia-induced chromatin context and in particular hypoxia-induced H3K9me3 include the repression of APAK, a negative regulator of p53. Activation of p53 is a key consequence of the hypoxia-induced DDR. Here we found that SETDB1, one of the H3 methyltransferases induced by hypoxia, mediates APAK repression. We propose that H3K9me3 plays a role in regulating APAK expression to allow optimal induction of p53 dependent apoptosis in hypoxic conditions suggesting a further role for H3K9me3 in facilitating DDR signalling in hypoxia. Together, these data suggest that the hypoxic chromatin context is critical for the role of the DDR as a barrier to tumourigenesis and predict that altering the chromatin landscape in combination with DNA damaging therapies would be efficacious in the treatment of hypoxic tumours.

Condition based monitoring of Thermal Protection Systems (TPS) is necessary for safe operations of space shuttles. In the current research Terahertz radiation (T-ray) has been used to detect mechanical and heat induced damages in TPS tiles. Voids and cracks inside the foam tile are denoted as mechanical damage while property changes due to long and short term exposures of tiles to high heat are denoted as heat induced damage.Ultrasonic waves cannot detect cracks and voids inside the tile because the tile material (silica foam) has high attenuation for ultrasonic energy. Instead, electromagnetic terahertz radiation can easily penetrate into the foam material and detect the internal voids although this electromagnetic radiation finds it difficult to detect delaminations between the foam tile and the substrate plate. Thus these two technologies are complementary to each other for TPS inspection.Ultrasonic and T-ray field modeling in free and mounted tiles with different types of mechanical and thermal damages has been the focus of this research. Shortcomings and limitations of FEM method in modeling 3D problems especially at high-frequencies has been discussed and a newly developed semi-analytical technique called Distributed Point Source Method (DPSM) has been used for this purpose.A FORTRAN code called DPSM3D has been developed to model both ultrasonic and electromagnetic problems using the conventional DPSM method. DPSM has been extended from ultrasonic applications to electromagnetic to model THz Gaussian beams, multilayered dielectrics and Gaussian beam-scatterer interaction problems. Since the conventional DPSM has some drawbacks, to overcome it two modification methods called G-DPSM and ESM have been proposed.The conventional DPSM in the past was only capable of solving time harmonic (frequency domain) problems. In this research DPSM has been extended to model DPSM transient problems. This modified technique has been denoted as t-DPSM.Using DPSM, scattering of focused ultrasonic fields by single and multiple cavities in fluid&solid media is studied. A comparison between the radiation forces generated by the ultrasonic energies reflected from two small cavities versus a single big cavity is also carried out.

Quantitative risk assessments are a fundamental part of economic analysis and natural hazard risk management models. It increases the objectivity and the transparency of risk assessments and guides policymakers in making efficient decisions when spending public resources on risk reduction. Managing hazard risks calls for an understanding of the relationships between hazard exposure and vulnerability of humans and assets.   The purpose of this thesis is to identify and estimate causal relationships between hazards, exposure and vulnerability, and to evaluate the applicability of systematically collected data sets to produce reliable and generalizable quantitative information for decision support.   Several causal relationships have been established. For example, the extent of lake flood damage to residential buildings depends on the duration of floods, distance to waterfront, the age of the house and in some cases the water level. Results also show that homeowners private initiative to reduce risk, prior to or during a flood, reduced their probability of suffering building damage with as much as 40 percent. Further, a causal relationship has been established between the number of people exposed to quick clay landslides and landslide fatalities.   Even though several relationships were identified between flood exposure and vulnerability, the effects can only explain small parts of the total variation in damages, especially at object level. The availability of damage data in Sweden is generally low. The most comprehensive damage data sets in Sweden are held by private insurance companies and are not publicly available. Data scarcity is a barrier to quantitative natural hazard risk assessment in Sweden. More efforts should therefore be made to collect data systematically for modelling and validating standardized approaches to quantitative damage estimation. / Natural hazard damages have increased worldwide. Impacts caused by hydrological and meteorological hazards have increased the most. An analysis of insurance payments in Sweden showed that flood damages have been increasing in Sweden as well. With climate change and increasing populations we can expect this trend to continue unless efforts are made to reduce risk and adapt communities to the threats. Economic analysis and quantitative risk assessments of natural hazards are fundamental parts of a risk management process that can support policymakers' decisions on efficient risk reduction. However, in order to develop reliable damage estimation models knowledge is needed of the relationships between hazard exposure and the vulnerability of exposed objects and persons. This thesis has established causal relationships between residential exposure and flood damage on the basis of insurance data. I also found that private damage-reducing actions decreased the probability of damage to buildings with almost 40 percent. Further, a causal relationship has been established between the number of people exposed to quick clay landslides and fatalities. Even though several relationships have been identified between flood exposure and vulnerability, the effects can explain only small parts of the total variation in damages, especially at object level, and more effort is needed to develop quantitative models for risk assessment purposes.

Many anticancer therapies, including radiotherapy, act by damaging the deoxyribosenucleic acid (DNA) that is fundamental to cell function and proliferation. H2AX is a histone protein associated with DNA that is phosphorylated to produce γH2AX in response to DNA double strand breaks (DSBs), the most lethal lesions caused in cancer cells. This thesis examines the translation of γH2AX detection assays to clinical situations in order to provide biomarkers of response that might help to guide the treatment of cancer patients. γH2AX immunohistochemistry was developed in preclinical xenograft models, and validated over a range of radiation doses and over time after irradiation. The method was prepared for translation to archived clinical biopsy and surgical specimens. The DSB Biomarkers Pilot Study was established in order to develop a method for γH2AX quantification in direct tumour cell specimens obtained using the clinical technique of fine needle aspiration (FNA) cytology. Eleven patients undergoing anticancer therapy were recruited to the study, and the method evaluated. The coefficient of variation of the measure was 49%. Non-invasive imaging for γH2AX would allow DNA damage to be quantified in all tumour sites, and on multiple occasions. An antibody-based nuclear medicine imaging agent was re-engineered using Fab fragments of the antibody. The novel agent demonstrated improved pharmacokinetics when compared to the whole antibody agent, but reduced target specificity. The findings further develop the potential to exploit DNA damage biomarker measurements in clinical oncology.

The topic of this Master's degree thesis is "Comparison of the legislation of the damage liability in the Czech and Austrian civil law". The purpose of the thesis is to give the general summary of the topic and to point out the main differences and similarities in the area of damage liability in the Czech and Austrian civil law. The core of the thesis consists in the comparison of the tort liability, i.e. damage liability arising from the illegal act (tort law) and the strict liability. The thesis should also verify, if the legislation of the damage liability in the traditional Austrian Code - Civil Code of Austria - is similar to the legislation in the Civil Code of the Czech Republic and if the Civil Code of Austria was an inspiration for the new Czech Civil Code. The thesis is composed of six chapters, the core could be found in the chapter two, four and five. Chapter One is a historical introduction and it describes the evolution of the civil law in the Austrian and Czech area. Chapter two is focused on the basic terminology and the key terms such as "damage liability" and "damages" and the constitution conditions of the damage liability as well as damages. The chapter gives a description of the main differences and similarities in the terminology in the both Codes. Chapter three examines the...

A research report submitted in partial fulfilment of the requirements for the degree of Master of Arts in Social and Psychological Research to the Department of Psychology, School of Human and Community Development, The University of the Witwatersrand, Johannesburg, South Africa, 2017 / Introduction. The provision of appropriate long term care facilities for people with acquired brain injury is a portentous issue internationally. There is a global lack of long term care facilities for people with acquired brain injury and they are often placed in facilities for the physically disabled or the elderly. It is unclear whether these facilities are suitable and what effect they may have on well-being and social isolation. Aim. This interpretive phenomenological study explored how adults with acquired brain injury experience living in such long term care facilities. Additionally, it described how such living arrangements impact on social isolation, a particularly devastating psychosocial consequence of acquired brain injury. Method. One-on-one, semi-structured interviews were conducted with seven adults who had acquired a brain injury. Each participant had been living in a long term care facility for at least one year. They were asked questions related to their general lived experience as well as specific questions to explore their experience of social isolation. Findings. Thematic content analysis of the interview data led to the following five categories of themes: overall evaluations (guarded approval, and disapproval); general lived experience (autonomy, choice, freedom, burden, boredom, and basic needs); social isolation (loneliness, companionship, and belonging); sources of isolation (living with the disabled, different disability, age differences, pets, and facility setup); and sources of well-being (positivity, and meaning). The main findings were that the general lived experience of people with ABI was mainly negative. The facilities generally met only basic needs and seldom met higher level psychological needs. Social isolation was commonly reported among residents with ABI in long term care facilities and was linked to age differences and having a brain injury in a facility geared for people with other disabilities. The findings were understood in relation to Bronfenbrenner’s ecological systems theory and Maslow’s hierarchy of needs. Conclusions. The findings of this study contribute towards filling a theoretical gap in understanding the lived experience of people with ABI in long term care facilities and how this contributes to social isolation. The findings have potential value to family members of people with acquired brain injury considering various living arrangement options. They can also be useful for long term care facilities housing people with brain injury to make changes that may result in greater well-being of their residents. / MT 2018

A Mecânica do Dano Contínuo é atualmente uma poderosa ferramenta para se modelar o comportamento não-linear de vários materiais decorrente da evolução de um processo de microfissuração. A perda de rigidez causada pelo processo físico tem sido considerada em modelos constitutivos através de variáveis de dano escalar, vetorial ou tensorial. Quando o carregamento é proporcionalmente crescente as deformações residuais podem ser ignoradas e relações constitutivas simples podem ser obtidas, onde os efeitos do dano aparecem por uma penalização direta das propriedades elásticas. Por outro lado, efeitos de dano podem ser acoplados com deformações residuais levando a relações constitutivas mais gerais. Esse trabalho está relacionado a esses tipos de modelos assumindo que o meio ideal apresenta um comportamento elástico linear com danificação ou elastoplástico com danificação. Um dos principais aspectos discutido relaciona-se à formulação variacional, a qual está baseada em conceitos de Análise Convexa e Não-Convexa. Explorando o fato que a evolução do dano tem correspondência com a idealização de regime de encruamento negativo, a teoria de localização de deformação é abordada e um estudo da condição necessária de singularidade ou perda da condição de elipticidade é realizado. Na sequência, uma proposta preliminar para uma análise de pós-singularidade, baseada na Teoria de Bifurcação, é feita no sentido de caracterizar pontos limite ou pontos de bifurcação de solução, em sistemas conservativos. / Continuum Damage Mechanics is nowadays a powerful tool to model the non-linear behaviour of several materials due to evolution of a microcracking process. The lost of rigidity caused by such physical process has been accounted in the constitutive models through a scalar, vectorial or tensorial damage variables. When proportional loading is considered the residuals strains can be ignored and simple constitutive relations can be obtained in which damage effects appear by direct penalization of the elastic properties. On the other hand, damage effects can be coupled with residual strains leading to more general constitutive relations. This work is related to such kind of models assuming that the ideal medium presents a linear elastic-damage or an elastoplastic-damage behaviour. One of the main topics discussed is related to the variational formulation which is based on Convex and Non-Convex Analysis concepts. Exploring the fact that damage evolution has correspondence with a softening idealised regime, the strain localization theory is treated and a study of a necessary condition for singularity or ellipticity tose condition is developed. In the sequence, a introductory poscritical analysis is proposed, based in the bifurcation theory and aiming to detect if the singularity corresponds to a limit or a bifurcation point solution, in conservative systems.