Seismic damage detection for a steel braced frame structure

A new approach for global detection of seismic damage in a single-storey steel concentrically braced frame (CBF) structure is presented. The filtered lateral in-plane acceleration response of the CBF structure is integrated twice to provide the lateral in-plane displacement which is used to infer buckling and yielding damage. The level of interstorey drift of the CBF during a seismic excitation allows the yield and buckling of the bracing members to be identified and indirectly detects damage based on exceedance of calculated lateral in-plane displacement limits. A band-pass filter removes noise from the acceleration signal followed by baseline correction being used to reduce the drift in velocity and displacement during numerical integration. This pre-processing results in reliable numerical integration of the frame acceleration that predicts the displacement response accurately when compared to the measured lateral displacement of the CBF structure. Importantly, the structural damage is not assumed through removal of bracing members, rather damage is induced through actual seismic loading. The buckling and yielding displacement threshold limits used to identify damage are demonstrated to accurately identify the initiation of buckling and yielding.

Brca1 and brca2:Role in the DNA damage response, cancer formation and treatment

BRCA1 and BRCA2 are highly penetrant breast and ovarian cancer susceptibility genes that are mutated in a significant proportion of familial breast and ovarian cancer syndromes. Both of these genes are tumour suppressors, the products of which play vital roles in the cellular response to DNA damage. These proteins function in a number of cellular pathways in order to maintain genomic stability including DNA damage signaling, DNA repair, cell cycle regulation, protein ubiquitination, chromatin remodeling, transcriptional regulation and apoptosis. This chapter will discuss the functions of these proteins and how they relate to tumour development, and therapy. © 2009 Springer Science+Business Media B.V.

Impact of average household income and damage exposure on post-earthquake distress and functioning: A community study following the February 2011 Christchurch earthquake.

Post-traumatic stress, depression and anxiety symptoms are common outcomes following earthquakes, and may persist for months and years. This study systematically examined the impact of neighbourhood damage exposure and average household income on psychological distress and functioning in 600 residents of Christchurch, New Zealand, 4–6 months after the fatal February, 2011 earthquake. Participants were from highly affected and relatively unaffected suburbs in low, medium and high average household income areas. The assessment battery included the Acute Stress Disorder Scale, the depression module of the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder Scale (GAD-7), along with single item measures of substance use, earthquake damage and impact, and disruptions in daily life and relationship functioning. Controlling for age, gender and social isolation, participants from low income areas were more likely to meet diagnostic cut-offs for depression and anxiety, and have more severe anxiety symptoms. Higher probabilities of acute stress, depression and anxiety diagnoses were evident in affected versus unaffected areas, and those in affected areas had more severe acute stress, depression and anxiety symptoms. An interaction between income and earthquake effect was found for depression, with those from the low and medium income affected suburbs more depressed. Those from low income areas were more likely, post-earthquake, to start psychiatric medication and increase smoking. There was a uniform increase in alcohol use across participants. Those from the low income affected suburb had greater general and relationship disruption post-quake. Average household income and damage exposure made unique contributions to earthquake-related distress and dysfunction.

Plasmid DNA damage following exposure to atmospheric pressure non-thermal plasma: kinetics and influence of oxygen admixture

The nature and kinetics of plasmid DNA damage after DNA exposure to a kHz-driven atmospheric pressure nonthermal plasma jet has been investigated. Both single-strand break (SSB) and double-strand break (DSB) processes are reported here. While SSB had a higher rate constant, DSB is recognized to be more significant in living systems, often resulting in loss of viability. In a helium-operated plasma jet, adding oxygen to the feed gas resulted in higher rates of DNA DSB, which increased linearly with increasing oxygen content, up to an optimum level of 0.75% oxygen, after which the DSB rate decreased slightly, indicating an essential role for reactive oxygen species in the rapid degradation of DNA.

Concrete damage plasticity model for modeling FRP-to-concrete bond behavior

The technique of externally bonding fiber-reinforced polymer (FRP) composites has become very popular worldwide for retrofitting existing reinforced concrete (RC) structures. Debonding of FRP from the concrete substrate is a typical failure mode in such strengthened structures. The bond behavior between FRP and concrete thus plays a crucial role in these structures. The FRP-to-concrete bond behavior has been extensively investigated experimentally, commonly using a single or double shear test of the FRP-to-concrete bonded joint. Comparatively, much less research has been concerned with numerical simulation, chiefly due to difficulties in the accurate modeling of the complex behavior of concrete. This paper presents a simple but robust finite-element (FE) model for simulating the bond behavior in the entire debonding process for the single shear test. A concrete damage plasticity model is proposed to capture the concrete-to-FRP bond behavior. Numerical results are in close agreement with test data, validating the model. In addition to accuracy, the model has two further advantages: it only requires the basic material parameters (i.e., no arbitrary user-defined parameter such as the shear retention factor is required) and it can be directly implemented in the FE software ABAQUS.

Finite element modelling of FRP-to-concrete bond behaviour using the concrete damage plasticity theory combined with a plastic degradation model

The technique of externally bonding fibre reinforced polymer (FRP) composites has been becoming popular worldwide for retrofitting existing reinforced concrete (RC) structures. A major failure mode in such strengthened structures is the debonding of FRP from the concrete substrate. The bond behaviour between FRP and concrete thus plays a crucial role in these structures. The FRP-to-concrete bond behaviour has been extensively investigated experimentally, commonly using the pull-off test of FRP-to-concrete bonded joint. Comparatively, much less research has been concerned with the numerical simulation of this bond behaviour, chiefly due to difficulties in accurately modelling the complex behaviour of concrete. This paper proposes a robust finite element (FE) model for simulating the bond behaviour in the entire loading process in the pull-off test. A concrete damage plasticity model based on the plastic degradation theory is proposed to overcome the weakness of the elastic degradation theory which has been commonly adopted in previous studies. The model produces results in very close agreement with test data. © Tsinghua University Press, Beijing and Springer-Verlag Berlin Heidelberg 2011.

Closure to “Concrete Damage Plasticity Model for Modeling FRP-to-Concrete Bond Behavior” by Y. Tao and J. F. Chen

The authors appreciate the discusser’s interest in the original paper and for the valuable discussion, which provides the opportunity to clarify and reiterate a few points made in the original paper. The comments and questions raised by the discusser are addressed in the following sections.

DNA mismatch repair and the DNA damage response to ionizing radiation:making sense of apparently conflicting data

The DNA mismatch repair (MMR) pathway detects and repairs DNA replication errors. While DNA MMR-proficiency is known to play a key role in the sensitivity to a number of DNA damaging agents, its role in the cytotoxicity of ionizing radiation (IR) is less well characterized. Available literature to date is conflicting regarding the influence of MMR status on radiosensitivity, and this has arisen as a subject of controversy in the field. The aim of this paper is to provide the first comprehensive overview of the experimental data linking MMR proteins and the DNA damage response to IR. A PubMed search was conducted using the key words "DNA mismatch repair" and "ionizing radiation". Relevant articles and their references were reviewed for their association between DNA MMR and IR. Recent data suggest that radiation dose and the type of DNA damage induced may dictate the involvement of the MMR system in the cellular response to IR. In particular, the literature supports a role for the MMR system in DNA damage recognition, cell cycle arrest, DNA repair and apoptosis. In this review we discuss our current understanding of the impact of MMR status on the cellular response to radiation in mammalian cells gained from past and present studies and attempt to provide an explanation for how MMR may determine the response to radiation.

Targeting of photooxidative damage on single-stranded DNA representing the bcr-abl chimeric gene using oligonucleotide-conjugates containing [Ru(phen)3](2+)-like photosensitiser groups

Photooxidative damage was induced predominantly at a single guanine base in a target DNA by irradiation (lambda > 330 nm) in the presence of complementary oligodeoxynucleotide conjugates (ODN-5'-linker-[Ru(phen)3]2+) (phen = 1,10-phenanthroline). The target DNA represents the b2a2 variant of the chimeric bcr-abl gene implicated in the pathogenesis of chronic myeloid leukaemia, and the sequence of the 17mer ODN component of the conjugate (3' G G T A G T T A T T C C T T C T T 5') was complementary to the junction region of the sense strand sequence of this oncogene. Two different conjugates were prepared, both of them by reaction of the appropriate succinimide ester with 5'-hexylamino-derivatised 17mer ODN. In Ru-ODN-1 (7) the linker was -(CH2)6-NHCO-bpyMe (-bpyMe = 4'-[4-methyl-2,2'-bipyridyl]), whereas in Ru-ODN-2 (13) it was -(CH2)6-NHCO-(CH2)3-CONH-phen. Photoexcitation of either of the conjugates when hybridised with the 32P-5'-end-labelled target 34mer 5'T G A C C A T C A A T A A G G A A G A A G21 C C C T T C A G C G G C C 3' (ODN binding site underlined) led to an alkali-labile site predominantly (> 90%) at the G21 base, which is at the junction of double-stranded and single-stranded regions of the hybrid. Greater yields were found with Ru-ODN-1 (7) than with Ru ODN-2 (13). In contrast to this specific cleavage with Ru-ODN-1 (7) or Ru-ODN-2 (13), alkali-labile sites were generated at all guanines when the 34mer was photolysed in the presence of the free sensitiser [Ru(phen)3]2+. Since [Ru(phen)3]2+ was shown to react with 2'-deoxyguanosine to form the diastereomers of a spiroiminodihydantoin derivative (the product from 1O2 reaction), 1O2 might also be an oxidizing species in the case of Ru-ODN-1 (7) and Ru-ODN-2 (13). Therefore to determine the range of reaction, a series of 'variant' targets was prepared, in which G21 was replaced with a cytosine and a guanine substituted for a base further towards the 3'-end (e.g. Variant 3; 5'T G A C C A T C A A T A A G G A A G A A C C G23 C T T C A G C G G32 C C3'). While it was noted that efficient reaction took place at distances apparently remote from the photosensitiser (e.g at G32, but not G23 for Variant 3), this effect could be attributed to hairpinning of the single-stranded region of the target. These results are therefore consistent with the photooxidative damage being induced by a reaction close to the photosensitiser rather than by a diffusible species such as 1O2.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.

Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and PPi. Although dUTP is a normal intermediate in DNA synthesis, its accumulation and misincorporation into DNA is lethal. Importantly, uracil misincorporation is a mechanism of cytotoxicity induced by fluoropyrimidine chemotherapeutic agents including 5-fluorouracil (5-FU) and elevated expression of dUTPase is negatively correlated with clinical response to 5-FU-therapy. In this study we performed the first functional characterization of the dUTPase promoter and demonstrate a role for E2F-1 and Sp1 in driving dUTPase expression. We establish a direct role for both mutant and wild-type forms of p53 in modulating dUTPase promoter activity. Treatment of HCT116 p53(+/+) cells with the DNA-damaging agent oxaliplatin induced a p53-dependent transcriptional downregulation of dUTPase not observed in the isogenic null cell line. Oxaliplatin treatment induced enrichment of p53 at the dUTPase promoter with a concomitant reduction in Sp1. The suppression of dUTPase by oxaliplatin promoted increased levels of dUTP that was enhanced by subsequent addition of fluoropyrimidines. The novel observation that oxaliplatin downregulates dUTPase expression may provide a mechanistic basis contributing to the synergy observed between 5-FU and oxaliplatin in the clinic. Furthermore, these studies provide the first evidence of a direct transcriptional link between the essential enzyme dUTPase and the tumor suppressor p53.

Using Instrumented Vehicles To Detect Damage in Bridges

Bridge structures are subject to continuous degradation due to the environment, ageing and excess loading. Monitoring of bridges is a key part of any maintenance strategy as it can give early warning if a bridge is becoming unsafe. This paper will theoretically assess the ability of a vehicle fitted with accelerometers on its axles to detect changes in damping of bridges, which may be the result of damage. Two vehicle models are used in this investigation. The first is a two degree-of-freedom quarter-car and the second is a four degree-of-freedom halfcar. The bridge is modelled as a simply supported beam and the interaction between the vehicle and the bridge is a coupled dynamic interaction algorithm. Both smooth and rough road profiles are used in the simulation and results indicate that changes in bridge damping can be detected by the vehicle models for a range of vehicle velocities and bridge spans.

Using Instrumented Vehicles to Detect Damage in Bridges

This paper describes a ‘drive-by’ method of bridge inspection using an instrumented vehicle. Accelerometers on the vehicle are proposed as a means of detecting damage on the bridge in the time it takes for the vehicle to cross the bridge at full highway speed. For a perfectly smooth road profile, the method is shown to be feasible. Changes in bridge damping, which is an indicator of damage, are clearly visible in the acceleration signal of a quarter-car vehicle on a smooth road surface modelled using MatLab. When road profile is considered, the influence of changes in bridge damping on the vehicle acceleration signal is much less clear. However, when a half-car model is used on a road with a rough profile, it is again possible to detect changes in bridge damping, provided the vehicle has two identical axles.