Towards the development of design tools for fatigue life assessment of composite structures

The threat of delaminations arising during in-service loading conditions is one of the key factors limiting the use of composite materials in large volume for main structures. Delamination occurrence is primarily caused by the interlaminar tension and shear stresses that develop due to different factors. These include geometric or materials discontinuities (e.g. edges, holes, dropped ply), but are also linked to internal mechanism failure, such as matrix cracks. The present thesis focuses on the investigation of the correlation existing between different damage mechanisms occurring in composite laminates. The problem of delamination initiation from transverse cracks in cross-ply laminates under quasi-static loading is thoroughly studied in Chapter 2. An analytical solution is presented for the local mode I, II and III stress fields arising in the close neighbourhoods of a transverse crack, stresses being written as a function of Generalised Stress Intensity Factors (GSIFs). Moreover, a fracture criterion for the delamination onset in cross-ply laminates under tension, based on a critical value for the mode 1 GSIF, is proposed and validated taking advantage of the results from an experimental campaign. The analytical solution describing the stress fields in the adjacencies of a transverse crack, found for cross-ply laminates, was then extended to be suitable to describe the stress fields for laminates with generic orientation (Chapter 3). The results of the research activity focused on the investigation of delamination evolution for composite laminates subjected to cyclic loads are presented in the following chapters. In particular, the outcomes of the experimental tests carried out on glass/epoxy cross ply laminates are presented in Chapter 4. Numerical analyses were performed to characterize the evolution of delamination area during fatigue life. Energy release rates (ERR) associated with delamination growth was calculated by using the virtual crack closure technique (VCCT) and a Paris-like curve was derived (Chapter 5). Furthermore, the reduction of Young's modulus and Poisson's ratio were modelled. Theoretical predictions were found to be consistent with collected experimental data. The process of delamination growth may be affected by different parameters. The presence of the friction sliding between the delaminated interfaces is one of these. The friction effects on ERR values are discussed in the Appendix. Different conditions of damage were numerically simulated, varying the value of the coefficient of friction and the length of delaminations. It was found that the presence of friction was not so influent for the purposes of delamination growth assessment. Then, with the aim of investigating damage evolution for laminates characterized by different orientations, fatigue tests were carried out on [0/452/-452]s and [0/452]s laminates. The different phases of the damage process were documented by collecting a detailed series of images, showing the accumulation of the observed failure modes. During the tests, the Young’s modulus and the Poisson’s ratio evolution were determined and their correlation with the damage evolution was investigated (Chapter 6). Following the approach used for cross-ply laminates, a correlation between the growth rate of delamination and ERR was investigated. Furthermore, a series of numerical investigations in response to the free edge delamination problem was performed. In fact, delamination initiation and growth was observed to occur more extensively near the free edges, both for balanced and unbalanced configuration of laminates. The results of these FE analyses are presented in Chapter 7. Finally, a model based on a probabilistic approach for the prediction of fibre failure of 0° laminae in cross ply laminates subjected to tensile-tensile fatigue loading will be described in Chapter 8

Caracterização funcional de uma globina putativa codificada pelo Gene Hsero_2872 de Herbaspirillum seropedicae SMR1

Resum

Therapeutic Ultrasounds: Physical Basis and Clinical Assessment

Improving quality in US physiotherapeutical treatments is mandatory in order to get ‘evidence‐based’ clinical results. This implies quality assurance protocols for the equipment, as well as some tentative dosimetrical approaches to predict local heating in joints following US parameter setting and operative modality. Finally, the possibility of ‘personalized therapy’ with multimodal (by qualitative and quantitative, e.g. based on sonography) assessment is discussed

Anti-bacterial prenylated phenols from the Kurdish medicinal plant Onobrychis carduchorum (Fabaceae)

Onobrychis carduchorum C.C. Towns. is a plant widely employed in the Kurdish traditional medicine, to cure inflammations and other skin diseases. We isolated ten different phenolic metabolites from an acetone extract of leaves and flowers. The phenolic compounds belong to three different classes, i.e.: 1. iso-flavones, having a genistein skeleton; 2. flavanones, bearing a naringenin skeleton; 3. dihydro-stilbenes. Many of them have a prenyl unit on an aromatic ring. The above compounds have been found to date mostly in other Fabaceae, as Glycyrrhiza glabra L. (liquorice)1. However, their bioactivities are largely unknown. In this work we reported a strong inhibition activity on the growth of Staphylococcus aureus, a well-known human pathogen. In particular, compound (Fig. 1) shows an inhibitory activity on growth, comparable to that of vancomycin, using the agar-diffusion standard method

Epidermal Growth Factor Receptor Gene in Primary Tumor and Metastatic Sites from Non-small Cell Lung Cancer

IntroductionThe majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.MethodsUsing fluorescence in situ hybridization (FISH) analysis, the EGFR gene status was evaluated in a series of 38 cerebral or adrenal metastases collected from two institutions and in the corresponding primary tumors. Also, EGFR mutational analysis was performed using direct sequencing on the cerebral metastases.ResultsEGFR FISH was positive in 28% of the primary tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH-positive at the metastatic site but negative in the primary tumor, six were brain metastases, and one was an adrenal metastasis; all were polysomic for chromosome 7, none were amplified. No EGFR mutations have been found in the cerebral metastases.ConclusionBecause the molecular asset of EGFR may change during the metastatic progression of NSCLC to brain (but not to adrenal), the selection of patients with brain metastasis for specific targeted therapies by EGFR FISH analysis should be performed on metastatic lesions rather than on their corresponding primary tumors

Activity of the EGFR-HER2 dual inhibitor afatinib in EGFR-mutant lung cancer patients with acquired resistance to reversible EGFR tyrosine kinase inhibitors

Background: The purpose of this study was to evaluate the efficacy of afatinib in EGFR-mutant metastatic NSCLC patients with acquired resistance to erlotinib or gefitinib. Materials and methods: We retrospectively analyzed the outcome of patients with EGFR-mutant advanced NSCLC treated with afatinib after failure of chemotherapy and EGFR TKIs. Results: A total of 96 individuals were included in the study. According to EGFR status, most patients (n = 63; 65.6%) harbored a deletion in exon 19, and de novo T790M mutation was detected in 2 cases (T790M and exon 19). Twenty-four (25%) patients underwent repeated biopsy immediately before starting afatinib and secondary T790M was detected in 8 (33%) samples. Among the 86 patients evaluable for efficacy, response rate was 11.6%, with a median progression free-survival (PFS) and overall survival (OS) of 3.9 and 7.3 months, respectively. No significant difference in PFS and OS was observed according to type of last therapy received before afatinib, type of EGFR mutation or adherence to Jackman criteria, and patients benefiting from afatinib therapy had longer PFS and OS (P &lt; .001). Outcome results for repeated biopsy patients were similar to the whole population, with no evidence of response in T790M-positive patients. All patients were evaluable for toxicity, and 81% experienced an AE of any grade, with grade 3 to 4 AEs, mainly diarrhea and skin toxicity, occurring in 19 (20%) patients. Conclusion: Our results showed that afatinib has only modest efficacy in a real life population of EGFR mutant NSCLC patients with acquired resistance to erlotinib or gefitinib