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Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit.Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR.Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively.The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUCgt;0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype.Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

The present work is concerned with adhesive bonding of thermoplastic composites used in general aerospace applications, including polyphenylene sulfide (PPS), polyetherimide (PEI) and polyetheretherketone (PEEK) carbon fibre composites. Three different surface treatments have been applied to the PEEK, PPS and PEI-based composites in order to enhance the adhesion: atmospheric plasma, ultraviolet radiation (UV) and isopropanol wiping as a control. Water contact angles and free surface energies were measured following the standard experimental procedure based on the employment of three different liquid droplets. Infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) were subsequently performed to characterize the surface chemistry of the samples after treatment. The single lap joints were manufactured and bonded by an Aerospace grade epoxy-based film adhesive originally developed for use on metals but with the ability to bond treated thermoplastics to good strength (supplied by Henkel Ireland). Quasi-static (QS) tests were conducted. The lap shear strength was evaluated, and the failure mechanisms of the different joints were examined for the range of surface treatments considered. It was found that the performances of the PEEK and PPS joints were considerably improved by the plasma and UV treatments resulting in cohesive and delamination failures, while PEI was unaffected by the plasma and UV treatments and performed very well throughout.

Ductile stainless steel fibres were used as interlayers to enhance the interlaminar fracture toughness of carbon fibre reinforced plastics (CFRPs). The stainless steel fibres were placed at the mid-plane of CFRPs either longitudinally or transversely to the crack growth direction . Mechanical properties and fracture toughness of the CFRPs were studied using uniaxial tensile test and double cantilever beam test , respectively. The Young’s modulus and tensile strength of CFRPs remained essentially the same due to the incorporation of steel fibres longitudinally to the loading direction, and decreased slightly for adding steel fibres transversely to the loading direction. Significant improvements in the fracture energy of CFRPs were achieved for adding stainless steel fibres, i.e. the mean fracture propagation energy increased from 482 J/m 2 for the control to 2295 J/m2 for CFRPs with transverse steel fibres at a density of 320 filaments/mm. The main toughening mechanisms of the steel fibres were investigated to be extensive steel fibre bridging and tensile failure. A more pronounced toughness increment was observed for adding steel fibres transversely to the crack growth direction due to the additional mechanisms of carbon fibre delamination and breakage.

This work studied the effects of adding short basalt fibers (BFs) and multi-walled carbon nanotubes (MWCNTs), both separately and in combination, on the mechanical properties, fracture toughness, and electrical conductivity of an epoxy polymer. The surfaces of the short BFs were either treated using a silane coupling agent or further functionalized by atmospheric plasma to enhance the adhesion between the BFs and the epoxy. The results of a single fiber fragmentation test demonstrated a significantly improved BF/epoxy adhesion upon applying the plasma treatment to the BFs. This resulted in better mechanical properties and fracture toughness of the composites containing the plasma-activated BFs. The improved BF/epoxy adhesion also affected the hybrid toughening performance of the BFs and MWCNTs. In particular, synergistic toughening effects were observed when the plasma-activated BFs/MWCNTs hybrid modifiers were used, while only additive toughening effects occurred for the silane-sized BFs/MWCNTs hybrid modifiers. This work demonstrated a potential to develop strong, tough, and electrically conductive epoxy composites by adding hybrid BF/MWCNT modifiers.

Interleaving thermoplastic veils has proved to enhance the interlaminar fracture toughness of carbon fibre/epoxy composites under static loading conditions. However, the fatigue delamination behaviour has yet to be investigated. Herein, meltable Polyamide-12 (PA) veils and non-meltable Polyphenylene-sulfide (PPS) veils were used for interlay toughening of unidirectional (UD) and non-crimp fabric (NCF) laminates that were manufactured using a prepreg process and resin transfer moulding process, respectively. The results of Mode-I fatigue delamination tests demonstrated a significant improvement in the fatigue life of the laminates due to interleaving. Additionally, the fatigue resistance energy has been maximumly increased by 143% and 190% for the UD and NCF laminates, respectively. The microscopy analysis revealed that the toughening mechanisms of thermoplastic veils were affected by the form of the thermoplastic veils in the laminates (melted or non-melted), the fracture mechanisms of the reference laminates and the adhesion/miscibility between the thermoplastic veils and the epoxy.

Interlaying thermoplastic veils into carbon fibre/epoxy composites has proved to significantly increase the interlaminar fracture toughness. The main toughening mechanism is thermoplastic fibre bridging for the non-meltable veils and matrix toughening for the meltable veils. Herein, to take advantage of different toughening mechanisms, hybrid meltable/non-meltable thermoplastic veils were used to interlay two types of aerospace-grade composites produced from unidirectional (UD) prepregs and resin transfer moulding of non-crimp carbon fibre fabrics (NCF). The mode-I and mode-II fracture behaviour of the interleaved laminates were investigated. The experimental results demonstrated outstanding toughening performance of the hybrid veils for the mode-I fracture behaviour of the UD laminates and for both of the mode-I and mode-II fracture behaviour of the NCF laminates, resulting from the combination of different toughening mechanisms. For example, the maximum increases in the mode-I and mode-II fracture energies of the NCF laminates were observed to be 273% and 206%, respectively.

Single-cell sequencing (SCS) is a powerful new tool that applies Next Generation Sequencing at the cellular level. SCS has revolutionized our understanding of tumor heterogeneity and the tumor microenvironment, immune infiltration, cancer stem cells (CSCs), circulating tumor cells (CTCs), and clonal evolution. The following chapter highlights the current literature on SCS in genitourinary (GU) malignancies and discusses future applications of SCS technology. The renal cell carcinoma (RCC) section highlights the use of SCS in characterizing the initial cells driving tumorigenesis, the intercellular mutational landscape of RCC, intratumoral heterogeneity (ITH) between primary and metastatic lesions, and genes driving RCC cancer stem cells (CSCs). The bladder cancer section will also illustrate molecular drivers of bladder cancer stem cells (BCSCs), SCS use in reconstructing tumor developmental history and underlying subclones, and understanding the effect of cisplatin on intratumoral heterogeneity in vitro and potential mechanisms behind platinum resistance. The final section featuring prostate cancer will discuss how SCS can be used to identify the cellular origins of benign prostatic hyperplasia and prostate cancer, the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, and the use of SCS in CTCs to understand chemotherapy resistance and gene expression changes after androgen deprivation therapy (ADT). The studies listed in this chapter illustrate many translational applications of SCS in GU malignancies, including diagnostic, prognostic, and treatment-related approaches. The ability of SCS to resolve intratumor heterogeneity and better define the genomic landscape of tumors and CTCs will be fundamental in the new era of precision-based care.

Carbonfibre reinforced poly-etherether-ketone (PEEK) and poly-phenylene-sulfide (PPS) composites were ra- pidly surface-treated by high-power UV light, and then adhesively bonded to aluminium 2024-T3 and carbonfibre/epoxy composites. The results of a single lap-shear joint test demonstrated that a UV-treatment lasting for 5 s was sufficient to prevent joint failure occurring at the composite/adhesive interfaces in all cases, e.g. it increased the failure strength of the PPS composite/aluminium joints from 11.1 MPa to 37.5 MPa. Moreover, the composite/adhesive interfaces performed well upon an exposure of the joints to an environment of high hu- midity and temperature for 8 weeks. Additionally, an investigation lasting for 6 months showed no degradation of the surface functionalisation from UV-irradiation. Overall, this work highlights high-power UV-irradiation a very promising method for surface preparation of thermoplastic composites (TPCs) for adhesive joining, i.e. TPC adhesive joints with excellent structural integrity can be obtained by using this rapid, eco-friendly and low-cost surface-treatment method.

Poly-etherether-ketone (PEEK) fibres (average diameter 30 μ m ) were surface-activated by a UV-irradiation technique, and then used as interlayers of carbon fibre/epoxy composites. The results of a flatwise tensile test demonstrated a significant improvement in the PEEK fibre/epoxy adhesion upon the UV-treatment, i.e. the ultimate strength increased from 0.6–0.7 MPa to 7.6 MPa. Accordingly, interlaying UV-irradiated PEEK fibres resulted in considerable increases in the maximum values of open-hole tensile strength, Charpy impact strength and mode-I fracture energy, i.e. of 12%, 131% and 293%, respectively. However, it also decreased the flexural strength by 29%, owing to the thickness increase caused by adding interlayers. Fortunately, the load carrying capacity (the maximum failure load under flexural bending) was largely unaffected, and moreover, an average residual strength of 475 ± 23 MPa still remained after the damage at the maximum load. The results demonstrated significant benefits of using longitudinal UV-irradiated PEEK fibres as interlayers of CFRPs.

The compatibility between the majority of thermoplastic veils (TPVs) and epoxies is typically poor, owing to the inherently low surface energies of thermoplastics. This tends to largely affect the toughening performance of TPVs as interlayer materials of carbonfibre/epoxy composites. The traditional methods for surface activation of thermoplastics, such as corona discharge, plasma treatment and acid etches, are not applicable to TPVs as they could cause significant damage to the thermoplasticfibres with nano-/micro-scale diameters. Herein, a UV- irradiation technique was proposed to active the surfaces of polyphenylene-sulfide (PPS) veils, that effectively improved their adhesion with epoxies. Consequently, the effects of an improved veil/epoxy adhesion on the mode-I and mode-II fracture behaviour and corresponding fracture mechanisms of the interleaved laminates were investigated. It was found that an improved veil/epoxy adhesion significantly enhanced the toughening performance of the PPS veils for the laminates manufactured by resin transfer moulding of non-crimp fabrics, by introducing additional carbonfibre delamination and significant PPSfibre damage during the fracture process. In contrast, the increased level of veil/epoxy adhesion inhibited PPSfibre bridging during the fracture process ofthe laminates produced from unidirectional prepregs, and caused considerable adverse effects on the fracture performance.

Polyphenylene-sulfide (PPS) veils doped with MWCNTs and graphene nanoplatelets (GNPs) were used as interleaves of a carbon fibre/epoxy composite, aiming to study its effects on the fracture performance. Interlaying original PPS veils significantly improved the mode-I and mode-II fracture toughness of the laminates due to a PPS fibre bridging mechanism. The addition of MWCNTs on the veils improved the PPS fibre/epoxy adhesion by introducing additional interactions, i.e. MWCNT pull-out and breakage, between the PPS fibres and the epoxy during the fracture process. This further improved the fracture toughness of the laminates at a relatively low content of MWCNTs. In contrast, the incorporation of GNPs on the veils decreased the PPS fibre/epoxy adhesion, resulting in detrimental effects on the fracture performance.

A high-power UV-irradiation technique was proposed for the surface treatment of PPS and PEEK composites, aiming to achieve good adhesion with epoxy adhesives. The composite substrates were rapidly UV-irradiated for a duration of between 2–30 s, and then bonded using an aerospace film adhesive to produce joints. Tensile lap-shear strength and mode-I and mode-II fracture energies of the adhesive joints were investigated. It was observed that the application of a short-time UV-irradiation to the substrates transformed the failure mode of the specimens from adhesion failure to substrate damage in all cases. This consequently resulted in remarkable improvements in the mechanical and fracture performance of the adhesive joints. For example, the lap-shear strength increased from 11.8MPa to 31.7MPa upon UV-irradiating the PPS composites for 3s, and from 8.3 MPa to 37.3 MPa by applying a 5 s UV-irradiation to the PEEK composites. Moreover, the mode-I and mode- II fracture energies significantly increased from∼50 J/m2to∼1500 J/m2and from&nbsp

Single-cell sequencing (SCS) is a powerful new tool that applies Next Generation Sequencing at the cellular level. SCS has revolutionized our understanding of tumor heterogeneity and the tumor microenvironment, immune infiltration, cancer stem cells (CSCs), circulating tumor cells (CTCs), and clonal evolution. The following chapter highlights the current literature on SCS in genitourinary (GU) malignancies and discusses future applications of SCS technology. The renal cell carcinoma (RCC) section highlights the use of SCS in characterizing the initial cells driving tumorigenesis, the intercellular mutational landscape of RCC, intratumoral heterogeneity (ITH) between primary and metastatic lesions, and genes driving RCC cancer stem cells (CSCs). The bladder cancer section will also illustrate molecular drivers of bladder cancer stem cells (BCSCs), SCS use in reconstructing tumor developmental history and underlying subclones, and understanding the effect of cisplatin on intratumoral heterogeneity in vitro and potential mechanisms behind platinum resistance. The final section featuring prostate cancer will discuss how SCS can be used to identify the cellular origins of benign prostatic hyperplasia and prostate cancer, the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, and the use of SCS in CTCs to understand chemotherapy resistance and gene expression changes after androgen deprivation therapy (ADT). The studies listed in this chapter illustrate many translational applications of SCS in GU malignancies, including diagnostic, prognostic, and treatment-related approaches. The ability of SCS to resolve intratumor heterogeneity and better define the genomic landscape of tumors and CTCs will be fundamental in the new era of precision-based care.

This study presents recent achievements in understanding the fracture behaviour of rubber-modified epoxy adhesives, notably the determination of the fully developed fracture process zone (FPZ) and its associated intrinsic fracture energy, G 0 . The shape and size of the FPZ are identified by inspecting the fracture surfaces using SEM, and exploring subsurface damage using optical microscopy and TEM. The thickness and failure strain of the FPZ are found to be essentially the same for different fracture tests, i.e. tapered double cantilever beam and single edge notched bending tests. As a consequence, the results from different fracture tests are linked by using the geometrically transferable, true fracture properties, i.e. FPZ thickness and G 0 . The variation of total fracture energy observed in different fracture tests is attributed to varying plastic deformation energy dissipated in plastic deformation zone (outside FPZ). The fracture behaviour of the adhesive is then successfully predicted by a cohesive zone model using parameters extracted from experiments.

Graphene nanoplatelets (GNP) were introduced into a rubber-modified epoxy adhesive in order to simultaneously improve the bulk mechanical properties, fracture toughness and single joint lap shear strength of the adhesive. The Young’s modulus was observed to increase marginally from 2.46 GPa to 2.56 GPa due to the addition of 0.1 wt.% GNPs. No further increase in modulus was observed for GNP loading above 0.1 wt.%. A negligible effect on the measured tensile strength was observed. The fracture energy of the bulk adhesive increased by 21 % due to the addition of 0.1 wt.% GNPs. No further increase in measured fracture energy was observed as the GNP content was further increased to 0.5 wt.%. A systematic decrease in the lap shear strength was observed due to the addition of GNPs, i.e. the lap shear strength decreased from 21.7 MPa of the control adhesive gradually to 17.2 MPa of the adhesive modified by 0.5 wt.% GNPs. Imaging analysis of the failed adhesive joints reveal that the reduction in lap shear strength was attributed to the preferential alignment of the GNPs in the direction parallel to the adhesive bonding surface. This was further confirmed by comparing the electrical behaviour of the lap shear joints with that of the bulk adhesive samples.

This paper critically examined the fracture behaviour of a rubber-modified, structural epoxy adhesive with various bond gap thicknesses ranging from 0.05 mm to 6 mm. The main and very novel contribution is direct measurement of the fracture process zone, plastic deformation zone and intrinsic fracture energy dissipated in the fracture process zone. The shape and size of the fracture process zone and plastic deformation zone were identified using scanning electron microscopy, transmission electron microscope and transmission optical microscope. As the bond gap thickness increased, the fracture energy increased steadily from 2365 J/m 2 for 0.05 mm bond gap thickness to 6289 J/m 2 of 1.6 mm bond gap thickness, and then plateaued. The thickness and failure strain of the fracture process zone remained essentially constant, being approximately 0.052 mm and 0.55 respectively, for different bond gap thicknesses. The intrinsic fracture energy (dissipated in the fracture process zone) appeared to be a material property, which remained approximately 2738 J/m 2 . The plastic deformation zone extended through the entire bond gap in thickness and occupied a significant length for all bond gap thicknesses. The effect of bond gap thickness on the fracture energy of the adhesive joints is hence directly attributed to the variation of the plastic deformation energy (dissipated in the plastic deformation zone) with bond gap thickness.

This paper presents a combined experimental and numerical study on the damage behaviour of core–shell rubber (CSR)-modified epoxy adhesives subject to high stress constraints. The test method consists of a notched axisymmetric adhesive layer loaded in tension. The stress–displacement curves of the rubber-modified adhesives have been found to exhibit a sudden reduction in stiffness after an initial linear loading region. It has been demonstrated that this corresponds to the cavitation of the rubber particles. The stress of rubber cavitation remained essentially constant at a critical hydrostatic stress of approximately 21 MPa over different rubber contents and different stress constraints. It is important to note that the rubber cavitation stress is also dependent on the size of the rubber particles, and the diameter of the rubber core is approximately 170 nm in current work. The stress constraint had negligible effect on the failure strength of the adhesive joints for the studied systems.

In this work the deformation behaviour of a nano-toughened epoxy adhesive is measured at different levels of stress triaxiality. The test method consists of a notched axisymmetric adhesive layer loaded in tension. The recorded traction displacement curves were analysed numerically and it was found that the measured peak stress corresponds to the intrinsic cohesive strength, σ max of the material. This method allows experimental measurement of σ max for use in cohesive zone models of fracture. Additional features of the traction displacement curves include a kink that corresponds to particle debonding at a critical hydrostatic stress. By application of the Mori–Tanaka model, the relationship between the experimental measurements and particle/matrix adhesion is described.

The bulk mechanical and fracture characterisation of an elastomer-toughened ethyl cyanoacrylate adhesive were investigated using thin film and standard double cantilever beam specimens, respectively. It is shown that these properties are strongly dependent on the prevailing curing conditions. These in turn are influenced by factors such as surface chemistry, curing time, the use of initiators, and the concentration of stabilizing acids in the system which have a profound effect on the polymerisation reaction. The curing conditions in turn have been shown to greatly influence the phase separation of the elastomeric toughening agent and the effectiveness of its associated toughening mechanism.

This paper reports on a dynamic mechanical analysis (DMA) study of carbon black filled, elastomer-toughened ethyl cyanoacrylate (ETECA) adhesive bulk films. The bulk films were cured at room temperature, both with and without premixed initiators, between poly (ethylene) (PE) substrates and in poly (tetrafluoroethylene) (PTFE) moulds. Adhesive batches with different strong and weak acid concentrations were used to study the influence of the curing speed on the phase separation behaviour of the elastomer. The mechanical properties of the bulk adhesive films and electron micrographs of the fracture surface of the tensile tested bulk specimens are reported in the previous publication by Ștefanov et al. [1; International Journal of Adhesion & Adhesives, 68: 142–155, 2016]. For all tested bulk adhesive films similar peaks were observed in the DMA curves, i.e., a peak at low temperature, before the glass transition region of the polymer, and a peak corresponding to the glass transition temperature of the poly (cyanoacrylate) adhesive. The results of this investigation show that the amount of the phase-separated elastomer increases with the increase in weak acid concentration for the samples cured without the use of initiators. An opposite trend was observed for the samples cured using initiators. Another important finding is that for a complete phase-separation of the elastomer from the poly CA a secondary step, following curing at room temperature, is necessary which should consist of heating the sample to 110 °C.

This work investigates the toughening performance of thermoplastic veils when used to interlay aerospace-grade CFRPs. Veils based on Polyethylene-terephthalate (PET), Polyphenylene-sulfide (PPS) and Polyamide-12 (PA) fibres ( ~ 10 μ m in diameter) were used as interlayers of unidirectional (UD), non-crimp fabric (NCF) and 5-Harness satin weave (5H) carbon fibre/epoxy laminates. During a hot curing process of the laminates, the PET and PPS veils remained in a fibrous form, and the PA veils melted. This resulted in different toughening mechanisms, i.e. interlaying the PET and PPS veils introduced extensive thermoplastic fibre bridging, and adding the PA veils improved the fracture toughness of the epoxy matrix. The different toughening mechanisms of the veils, together with the different fracture mechanisms of the laminates, dramatically affected the toughening levels. In general, the PET and PPS veils were more effective for toughening the UD laminates, and the PA veils were superior for the NCF and 5H laminates.

The effect of microstructure on the fracture properties of polycrystalline cubic boron nitride (PcBN) for industrial applications has been investigated numerically using the finite volume method. Representative synthetic microstructures have been created using a modified Voronoi tessellation procedure and these have been implemented in a multi-scale model to investigate the effect of individual microstructural parameters on the bulk material toughness. Crack initiation and propagation has been modelled using an arbitrary crack propagation solver using a cell-centred finite volume based method in FOAM-ext-3.0. The results demonstrate that individual microstructural parameters and their properties, such as percentage grains as well as precise traction–separation relationships between the phases, can greatly influence fracture behaviour and their contributions to the overall fracture toughness of PcBN is quantified and discussed.

A systematic study of the residual stress distribution in number of polycrystalline diamond grades was performed using Raman spectroscopy. The analysis focuses on evaluating the stress state in the specimen both before and after oil quench treatment, with a particular emphasis on the role of the second phase material. Prior to heat treatment, measurements along the surface of the specimen indicate an average residual stress in excess of 1.5 GPa for all grades examined. For specimens subjected to oil quenching at 600 °C an increase in the presence of tensile stress was recorded. The removal of the cobalt second phase from the surface of the microstructure had the effect of limiting this increase of tensile stresses on the specimen surface. Numerical modelling of the quench experiment was performed for polycrystalline diamond using the finite volume method (FV). The increase in residual stress, observed experientially after oil quenching was reproduced numerically, validating the experimental approach for approximating the stress distribution on the surface of the specimens.

Developing an understanding of the dominant failure mechanisms, and identifying the underlying structure–property relationship for polycrystalline diamond (PCD) are of fundamental importance for establishing a roadmap for the future design of materials with improved properties. In this paper, the Finite Volume (FV) method is used to generate representative PCD microstructures based on a diffuse-interface modelling approach. A cell-centred arbitrary crack propagation model is adopted to explore the strength and failure distribution of PCD as a function of the underlying microstructure. In particular, simulations are undertaken to identify the influence of phase morphology and individual constituent properties on the overall fracture strength of PCD. Results indicate that the morphology and distribution of the second phase cobalt relative to grain boundaries have a significant influence on the fracture strength of PCD. The stochastic nature of the strength of the individual grain boundaries was investigated. Larger variation in the distribution of interfacial bond strengths was found to result in a decrease in the overall strength for PCD grades. The effect of removing the cobalt from the microstructure was such that it reduced the overall strength but elevated the sensitivity to grain bond strength distribution. The presented work provides a framework for identifying the salient microstructural features, and offers a means for developing future grades of PCD through targeted virtual material design.

The fracture toughness of polycrystalline diamond has been investigated with reference to the microstructure. The physical interpretation of the critical distance is examined, and it is illustrated that this becomes increasingly difficult to define for larger grain sizes. Consequently, the minimum notch root radius becomes an important parameter governing the accuracy of toughness for blunt notched specimens. A higher than expected toughness was observed for fine grain specimens, illustrating the influence of the combination of both intrinsic and extrinsic fracture mechanisms on the overall toughness. Finally, the process of cobalt removal was found to reduce toughness compared to conventional grades.

The mode I fracture toughness of a single co-cured and two secondary bonded joint systems were determined using the double cantilever beam test. The initiation values of fracture toughness from the PTFE film insert and a mode I crack-tip were considered as well as propagation values. It was found that the starting defect had a large influence on the initiation values for fracture toughness. It was also found that the two secondary bonded systems predominantly resulted in cohesive failure while the co-cured joiailed interfacially. Thermogravimetric analysis coupled with mass-spectrometry was used to show how moisture in the composite prepreg and adhesive affected the toughness of the joints. Microscopy methods were used to gain further insight into the damage mechanisms of the three joint systems. Deposited by bulk import

Numerical investigations using the finite volume (FV) method were conducted to examine the effect of microstructure and mi- crostructural properties on the fracture strength of advanced ceramics with industrial applications. Statistically representative microstructural volumes were created using a diffuse-interface model using OpenFOAM-1.6-ext. Crack initiation and growth was modeled using a recently developed arbitrary crack propagation model. It was found that by varying the Young's modulus of the second phase material, a significant change in the maximum failure load was observed. It was also shown that there exists an opti- mum Young's modulus for which a maximum failure load will be reached. A number of microstructures with a varying percentage second phase material were investigated in this study. Results indicate that for a given set of material and cohesive parameters the maximum failure load was insensitive to the percentage second phase material. This study highlights the role that microstructure adconstituent properties of brittle ceramics have on influencing the fracture strength of such material. With this in mind, a para- metric study was undertaken to examine the competition between crack deflection and crack penetration at the interface between two materials. It was found that appropriate choice of interface strength and toughness as well as second phase material compliance was required in order to promote an overall strength and toughness increase through crack deflection and bridging. Such numerical modeling is essential in order to gain a greater understanding into the structure-property relationship that exists for such advanced ceramics. Deposited by bulk import

Two round robins on mode I fatigue delamination propagation organized by Technical Committee 4 of the European Structural Integrity Society compared three unidirectional carbon fiber reinforced composites, one with thermoplastic (poly-ether-ether-ketone) and two with thermoset (epoxy) matrix tested at five laboratories. Different approaches for data evaluation and their effect on the in- and inter-laboratory scatter are discussed and compared. Calculated delamination rates da/dN and applied GImax from displacement controlled tests are sensitive to small scatter in the load signal, and, therefore, a new route to evaluate the crack growth rate from pairs of load and displacement data is presented. Deposited by bulk import

Polyethylene terephthalate (PET) veils doped with and without multi-walled carbon nanotubes (MWCNT) were used to interlay a unidirectional carbon fibre/epoxy composite. The electrical and fracture properties of the laminates were studied. Significant improvements in the Mode-I fracture energy ( G I C ) and Mode-II fracture energy ( G I I C ) of the laminates were observed for interlaying the original PET veils. This was associated with a considerable drop in the electrical conductivity. Doping a small amount of MWCNTs on the PET interlayers strikingly improved the electrical conductivity of the laminates, especially in the through-thickness direction. However, it also resulted in moderate decreases in G I C and G I I C . Interestingly, this was caused by an improved PET fibre/epoxy adhesion due to the presence of the MWCNTs on the PET fibres, that restrained the PET fibre bridging in the fracture process. The experimental results demonstrated the potential of developing both highly electrically conductive and tough laminates by interlaying MWCNT-doped thermoplastic veils.

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had > 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.

A combined experimental–numerical method was used to investigate the role of microstructure on the fracture of advanced ceramics. In particular, the effect of grain size and matrix content were examined. Two dimensional representative finite volume (FV) microstructures were created using Voronoi tessellation to synthetically represent the microstructure of a two phase ceramic composite. It is shown, by comparing with real micrographs, that the method captures the features of real microstructures in terms of grain size distribution, grain aspect ratio and the distribution of second phase agglomerations. Simulation results indicate the computed elastic parameters are within the Hashin–Shtrikman bounds and also agree well with the Eshelby–Mori–Tanaka method. It is found that the underlying microstructure significantly affects the local stress and strain distributions in these advanced ceramics. Deposited by bulk import

Advanced ceramics are a class of material used in extreme conditions, such as high speed turning of aerospace alloys and rock drilling. Their high hardness makes them suitable for these uses, however their lower toughness means that failure due to fracture and chipping is a problem. They are composed of micron-sized particles of a primary hard phase together with either a ceramic or metallic matrix material. A combined experimental-numerical method was used to investigate the role of microstructure on the fracture of advanced ceramics. Two dimensional, statistically representative microstructures of the advanced ceramics are created using Voronoi tessellation. The synthetic microstructures are compared to real microstructures in terms of particle size distribution and particle aspect ratio. Simulation results indicate that the computed elastic parameters are within the Hashin-Shtrikman bounds and agree closely with analytical predictions made with the Eshelby-Mori-Tanaka method. It is found that the local sts and strain distribution within the model is significantly affected by the underlying microstructure, which in turn affects fracture properties. Hence, tailoring the microstructure can optimise the bulk strength parameters of the material. Deposited by bulk import

Advanced ceramics are a class of materials used as cutting tools in some of the most demanding material removal operations. Their high hardness makes them extremely suited for use at these extreme conditions. However they have a relatively low fracture toughness when compared to other conventional tool materials. A combined experimental-numerical method was used to investigate the role of microstructure on the fracture of advanced ceramics. In particular, the effect of grain size and matrix content were examined. Representative finite volume (FV) microstructures were created using Voronoi tessellation. It is shown, by comparing with real micrographs, that the method captures the features of real microstructures in terms of grain size distribution and grain aspect ratio. It was found that the underlying microstructure significantly affects the failure of this class of materials. Furthermore, it was found that by altering the microstructural parameters in the numerical model, such as grain size and matrix cont, it is possible to specify material improvements. Deposited by bulk import

An arbitrary crack propagation model using cell-centre nite volume based method is presented. Crack growth in an elastic solid, across an interface perpendicular to the initial crack path and into a second elastic solid is analysed. Crack initiation and the subsequent path of propagation are shown to arise naturally out of the selection of appropriate cohesive parameters. It is shown that the allowable crack propagation path is restricted by the underlying mesh. Results are presented for a number of values of interfacial strength and ratios of elastic properties between the two elastic solids. For higher values of interfacial strength, the crack is shown to propagate straight through the interface, while for lower values of interfacial strength, the crack is shown to change direction and propagate along the interface. It is shown that with careful selection of material and interface parameters it is possible to arrest a propagating crack at the interface. The method represents a useful step towards the prediction of crack propagation in complex structures. Other funder Element 6 Ltd and Enterprise Ireland Deposited by bulk import kpw7/11/13

Numerical modelling of a series of experimental Single Edge V-Notched Beam tests was carried out for a number of grades of polycrystalline cubic boron nitride using the finite volume method (FV) and cohesive zone model approach. The effect of notch root radius observed experimentally was reproduced numerically via a unique CZM for each material examined. It was also found that the shape of the cohesive zone model can be signiffcant, especially when the material has a relatively high fracture energy. It was also demonstrated that the experimentally observed drop in fracture toughness with increase in test rate was not explainable in terms of the system dynamics. It was found that in order to predict the experimental fracture loads for a range of loading rates, it was necessary to modify the CZM in such a way as to preserve the micro-structural length scale information of the material embedded within the CZM. Deposited by bulk import

The present work investigated the effect of the level of prepreg moisture content on the mixed-mode fracture toughness of a co-cured composite joint. It was found that moisture was stored in the prepreg as either free or bound water. It was also shown that the prepreg stores moisture from high humidity environments as free water, while the level of bound water remains unaffected. The excessive moisture was shown to plasticise the adhesive, lowering the glass transition temperature. The fracture toughness decreased under mode I and mode II loading as the humidity level was increased. The mixed-mode toughness also reduced with increasing storage humidity. However, the measured mixed-mode fracture toughness never reduced below that of the joints fabricated using the as-received material. This indicates that the moisture has a more pronounced effect on the bulk properties of the adhesive rather than on the interfacial adhesion between the composite and adhesive. Irish Research Council for Science, Engineering and Technology Other funder Cytec Engineered Materials (CEM) Deposited by bulk import kpw7/11/13

Polycrystalline diamond (PCD) materials are used in various applications, mainly as cutting tools for machining non-ferrous metals and non-metallic materials and for rock drilling operations. A better knowledge of their mechanical properties is of fundamental importance to PCD manufacturers and end users. In order to understand and predict the behaviour and structural integrity of the tools containing PCD, it is first necessary to study the behaviour of the material as a function of loading rate and temperature. In this paper, material behaviour is determined under testing conditions which correspond more closely to those in actual drilling, which is a significant improvement over investigations to date. Young’s modulus determined by four-point bending and a split-Hopkinson pressure bar apparatus was relatively constant with the rate, while a consistent decrease was observed with increase of temperature. The flexural strength was found to increase with the temperature, while decreasing with an increase in rate. Deposited by bulk import

The effect of thermal shock on the exural strength has been investigated experimentally. It was found that the variation in exural strength with quench temperature was influenced by the CBN grain size. Polycrystalline material containing small CBN grains showed a discontinuous drop in measured exural strength above a material dependent critical quench temperature difference, delta Tc. The sharp decrease in measured strength is accompanied by unstable crack propagation. Material containing a significantly larger CBN grain size, exhibited a gradual decrease in strength above the critical quench conditions. The experimental observations agreed with an established theory developed for thermal shock of alumina. The theoretically calculated critical temperatures agree well with the observed experimental data for each material when a aw size equal to the CBN grain size is employed. Deposited by bulk import

Polycrystalline Cubic Boron Nitride (PCBN) is a super-hard material, which is used in some of the most demanding material removal operations today. PCBN cutting tools are employed in turning of hardened steels as well as machining of other abrasive and aerospace grade alloys. In these applications the tools are subjected to high operating temperatures, abrasive and impact loading. Impact loading can lead to the sudden fracture and hence failure of the tool. Much of the recent developments in this industry have been focused on improving the fracture toughness of the PCBN compact. In this work a hypothesis based on induced thermal stresses at the crack tip has been put forward to explain the observed rate sensitivity of PCBN. The results show that the fracture toughness of PCBN is closely linked to the CBN grain size and that the rate sensitivity can be explained in part by induced thermal stresses at the crack tip at high rates of loading.

In the present study, the mixed-mode fracture toughness of an adhesively bonded composite joint system was examined using a variety of linear elastic fracture mechanics (LEFM) based tests. These tests include the mode I double cantilever beam (DCB), mixed-mode asymmetrical DCB (ADCB) and mode II end load split (ELS) test. The joint system was also evaluated using the wide area lap shear (WALS) test that is often employed by the aerospace industry. While lap shear type tests are relatively simple to perform and post-process compared to their LEFM counterparts, the results can often be misleading and are greatly dependent on the overlap length, thickness of substrate and type of fillet. The experimental tests were also simulated using OpenFOAM, a finite volume based software package. Through this combined experimental-numerical approach, a greater understanding of the influence of the peel ply surface treatment and scrim cloth on the behaviour of the WALS test was achieved.

Polycrystalline diamond compacts (PDC) cutters are widely used in oil and gas well drilling and a different format of the same material is also used in high speed turning. During the cutting process these tools experience very high temperatures and impact loads which lead to their sudden fracture. In this work the mechanical and fracture properties of two different grades of PCD test specimens, i.e. the Young’s modulus and fracture toughness, are measured under a range of test conditions such as temperature and loading rate, which correspond to the actual drilling conditions. The fracture is found to propagate in a highly dynamic manner, where the results show the examined properties of PCD specimens to vary with the loading rate and temperature. The study performed leads to a greater understanding of PCD behaviour, and aims to provide guidance for improved material design.