A field experiment on a steel Gerber-truss bridge for damage detection utilizing vehicle-induced vibrations

A field experiment was conducted on a real continuous steel Gerber-truss bridge with artificial damage applied. This article summarizes the results of the experiment for bridge damage detection utilizing traffic-induced vibrations. It investigates the sensitivities of a number of quantities to bridge damage including the identified modal parameters and their statistical patterns, Nair’s damage indicator and its statistical pattern and different sets of measurement points. The modal parameters are identified by autoregressive time-series models. The decision on bridge health condition is made and the sensitivity of variables is evaluated with the aid of the Mahalanobis–Taguchi system, a multivariate pattern recognition tool. Several observations are made as follows. For the modal parameters, although bridge damage detection can be achieved by performing Mahalanobis–Taguchi system on certain modal parameters of certain sets of measurement points, difficulties were faced in subjective selection of meaningful bridge modes and low sensitivity of the statistical pattern of the modal parameters to damage. For Nair’s damage indicator, bridge damage detection could be achieved by performing Mahalanobis–Taguchi system on Nair’s damage indicators of most sets of measurement points. As a damage indicator, Nair’s damage indicator was superior to the modal parameters. Three main advantages were observed: it does not require any subjective decision in calculating Nair’s damage indicator, thus potential human errors can be prevented and an automatic detection task can be achieved; its statistical pattern has high sensitivity to damage and, finally, it is flexible regarding the choice of sets of measurement points.

Identification of potentially pathogenic variants in candidate breast and ovarian cancer susceptibility genes in BRCAX patients

Mutations within the BRCA1 and BRCA2 genes account for approximately 20% of hereditary breast cancers, with a further 10%–15% being attributable to rare mutations in moderate-risk genes and common variants in low-risk genes. The genes harbouring mutations in the remaining ∼65% of hereditary breast cancers are unknown. The identification of mutation carriers in hereditary breast and ovarian cancer (hboc) families is critical for determining who is most at risk of developing the disease and therefore who should be offered risk-reducing procedures or more intensive screening, or both.

Many of the high- and moderate-risk genes for hereditary breast cancers encode proteins that work in concert to maintain genomic stability and in dna damage signalling and repair. A novel BRCA1 protein complex identified within the research group whose target genes are involved in dna repair provided novel candidates for hboc susceptibility genes. These 12 candidate genes were sequenced in a cohort of 675 affected individuals from the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) with hereditary breast or ovarian cancer, but with no mutations in known susceptibility genes (BRCAx patients). This analysis identified 20 individuals (each from a different BRCAx family) with different potentially pathogenic variants across 6 of the candidate hboc susceptibility genes. The family members of each BRCAx index case were tested for the presence of the specific mutation identified in the proband to examine segregation with disease. To further expand on the potential role of the novel candidate hboc susceptibility genes identified in this study, the genetic variation of a second cohort of 520 Northern Irish BRCAx patients is being characterized using a 61-gene panel.

Chemoprevention in BRCA1 Mutation Carriers—A Proof-of-Concept Study

Background: Women with germline BRCA1 mutations have a high lifetime risk of breast cancer, with the only available risk-reduction strategies being risk-reducing surgery or chemoprevention. These women predominantly develop triple-negative breast cancers; hence, it is unlikely that selective estrogen receptor modulators (serms) will reduce the risk of developing cancer, as these have not been shown to reduce the incidence of estrogen receptor–negative breast cancers. Preclinical data from our laboratory suggest that exposure to estrogen and its metabolites is capable of causing dna double-strand breaks (dsbs) and thus driving genomic instability, an early hallmark of BRCA1-related breast cancer. Therefore, an approach that lowers circulating estrogen levels and reduces estrogen metabolite exposure may prove a successful chemopreventive strategy.

Aims: To provide proof of concept of the hypothesis that the combination of luteinizing-hormone releasing-hormone agonists (lhrha) and aromatase inhibitors (ais) can suppress circulating levels of estrogen and its metabolites in BRCA1 mutation carriers, thus reducing estrogen metabolite levels in breast cells, reducing dna dsbs, and potentially reducing the incidence of breast cancer.

Methods: 12 Premenopausal BRCA1 mutation carriers will undergo baseline ultrasound-guided breast core biopsy and plasma and urine sampling. Half the women will be treated for 3 months with combination goserelin (lhrha) plus anastrazole (ai), and the remainder with tamoxifen (serm) before repeat tissue, plasma, and urine sampling. After a 1-month washout period, groups will cross over for a further 3 months treatment before final biologic sample collection. Tissue, plasma, and urine samples will be examined using a combination of immunohistochemistry, comet assays, and ultrahigh performance liquid chromatography tandem mass spectrometry to assess the impact of lhrha plus ai compared with serm on levels of dna damage, estrogens, and genotoxic estrogen metabolites. Quality of life will also be assessed during the study.

Results: This trial is currently ongoing.

Charge migration induced by attosecond pulses in bio-relevant molecules

After sudden ionization of a large molecule, the positive charge can migrate throughout the system on a sub-femtosecond time scale, purely guided by electronic coherences. The possibility to actively explore the role of the electron dynamics in the photo-chemistry of bio-relevant molecules is of fundamental interest for understanding, and perhaps ultimately controlling, the processes leading to damage, mutation and, more generally, to the alteration of the biological functions of the macromolecule. Attosecond laser sources can provide the extreme time resolution required to follow this ultrafast charge flow. In this review we will present recent advances in attosecond molecular science: after a brief description of the results obtained for small molecules, recent experimental and theoretical findings on charge migration in bio-relevant molecules will be discussed.