Finite element analysis of drilling of titanium alloy

Drilling is a highly demanding machining process due to complex tool geometry and the progressive material failure on the work piece. In this study, a 3D model is developed using commercial finite element software ABAQUS/Explicit. The proposed model simulates the drilling process by taking into account of the damage initiation and evolution of the work piece material, a contact model at the interface between drill bit and work piece and the process parameters. The results of the simulations demonstrate the effects of machining parameters on drilling. The results also confirm the capability and advantage of FE simulation of the drilling process. © 2011 Published by Elsevier Ltd.

Performance and wear of coated carbide drill in machining of carbon fibre reinforced composite/titanium stack

In this research we investigate the performance of drilling process in carbon fibre reinforced composite (CFC) material, titanium alloy and the hybrid stack of these two materials, using coated carbide drill bit. We study the effect of the process parameters such as the feed rate and speed on the induced forces and torques, also on the wear of drill and surface roughness of the holes. In the composite material the percentage of surface damage in both drilling CFC on its own and drilling in stack form is estimated. Also, the effect of worn drill on the surface damage is identified. In the titanium, the burr formation in stack and non-stack form is investigated. The wear of the drill results in increased forces and torques required for drilling. This increases the surface delaminations substantially at the entrance in drilling of CFC. However, the surface roughness of the holes reduces with the wear of the drill in CFC drilling. Also, the surface delamination and surface roughness of the holes in the CFC whilst drilled in hybrid form reduces significantly. This is despite the increase of the forces and torques required in drilling CFC in stack form. Copyright © 2012 Inderscience Enterprises Ltd.

Evaluation of drilling process in Ti6Al4V using 3D FE simulation

Drilling of Ti6Al4V is investigated experimentally and numerically. A 3D finite element model developed based on Lagrangian approach using commercial finite element software ABAQUS/explicit. 3D complex drill geometry is included in the model. The drilling process simulations are performed at the combinations of three cutting speed and four feed rates. The effects of cutting parameters on the induced thrust force and torque are predicted by the developed model. For validation purpose, experimental trials have been performed in similar condition to the simulations. The forces and torques measured during experiment are compared to the results of the finite element analysis. The agreement of the experimental results for force and torque values with the FE results is very good. Moreover, surface roughness of the holes was measured for mapping of machining. Copyright © 2013 Inderscience Enterprises Ltd.

Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

A multi-capability sensor for hydrocarbons, synthetic-based fluids and heavy metals:Applications for environmental monitoring during removal of drill cuttings piles

As part of any drilling cuttings pile removal process the requirement for monitoring the release of contaminants into the marine environment will be critical. Traditional methods for such monitoring involve taking samples for laboratory analysis. This process is time consuming and only provides data on spot samples taken from a limited number of locations and time frames. Such processes, therefore, offer very restricted information. The need for improved marine sensors for monitoring contaminants is established. We report here the development and application of a multi-capability optical sensor for the real-time in situ monitoring of three key marine environmental and offshore/oil parameters: hydrocarbons, synthetic-based fluids and heavy metal concentrations. The use of these sensors will be a useful tool for real-time in situ environmental monitoring during the process of decommissioning offshore structures. Multi-capability array sensors could also provide information on the dispersion of contamination from drill cuttings piles either while they are in situ or during their removal.

Holocene “turn-on” and evolution of the Southern Great Barrier Reef: Revisiting reef cores from the Capricorn Bunker Group

Extensive drilling of the Great Barrier Reef (GBR) in the 70s and 80s illuminated the main factors controlling reef growth during the Holocene. However, questions remain about: (1) the precise nature and timing of reef "turnon" or initiation, (2) whether consistent spatio-temporal patterns occur in the bio-sedimentologic response of the reef to Holocene sea-level rise then stability, and (3) how these factors are expressed in the context of the different evolutionary states (juvenile-mature-senile reefs). Combining 21 new C14-AMS and 146 existing recalibrated radiocarbon and U/Th ages, we investigated the detailed spatial and temporal variations in sedimentary facies and coralgal assemblages in fifteen cores across four reefs (Wreck, Fairfax, One Tree and Fitzroy) from the Southern GBR. Our newly defined facies and assemblages record distinct chronostratigraphic patterns in the cores, displaying both lateral zonation across the different reefs and shallowing upwards sequences, characterised by a transition from deep (Porites/faviids) to shallow (Acropora/Isopora) coral types. The revised reef accretion curves show a significant lag period, ranging from 0.7-2 ka, between flooding of the antecedent Pleistocene substrate and Holocene reef turn-on. This lag period and dominance of more environmentally tolerant early colonizers (e.g., domal Porites and faviids), suggests initial conditions that were unfavourable for coral growth. We contend that higher input of fine siliciclastic material from regional terrigenous sources, exposure to hydrodynamic forces and colonisation in deeper waters are the main factors influencing initially reduced growth and development. All four reefs record a time lag and we argue that the size and shape of the antecedent platform is most important in determining the duration between flooding and recolonisation of the Holocene reef. Finally, our study of Capricorn Bunker Group Holocene reefs suggests that the size and shape of the antecedent substrate has a greater impact on reef evolution and final evolutionary state (mature vs. senile), than substrate depth alone. 

Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system:a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro

BACKGROUND: We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.

METHODS: We developed a pair of vectors, containing either five or eight copies of the hypoxia response element (HRE) isolated from the vascular endothelial growth factor (pH5VCD) or glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (pH8GCD) gene, respectively. The kinetics of the hypoxic induction of the vectors and sensitization effects were evaluated in 22Rv1 and DU145 cells in vitro.

RESULTS: The CD protein as selectively detected in lysates of transiently transfected 22Rv1 and DU145 cells following hypoxic exposure. This is the first evidence of GAPDH HREs being used to control a suicide gene therapy strategy. Detectable CD levels were sustained upon reoxygenation and prolonged hypoxic exposures. Hypoxia-induced chemoresistance to 5-FU was overcome in both cell lines treated with this suicide gene therapy approach. Hypoxic transfectants were sensitized to prodrug concentrations that were ten-fold lower than those that are clinically relevant. Moreover, the surviving fraction of reoxygenated transfectants could be further reduced with the concomitant delivery of clinically relevant single radiation doses.

CONCLUSIONS: This strategy thus has the potential to sensitize the hypoxic compartment of prostate tumours and improve the outcome of current therapies.

Solitary and repetitive binding motifs for the AP2 complex alpha-appendage in amphiphysin and other accessory proteins

Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery. This machinery interacts with the appendage domains of APs, which have platform and beta-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the alpha-appendage. The motif domain of amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the alpha-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the alpha-appendage.

Mining Money: the generative capacities of scientific and legal knowledge practices in the making of resource economies

In 1997 a scandal associated with Bre-X, a junior mining firm, and its prospecting activities in Indonesia, exposed to public scrutiny the ways in which mineral exploration firms acquire, assess and report on scientific claims about the natural environment. At stake here was not just how investors understood the provisional nature of scientific knowledge, but also evidence of fraud. Contemporaneous mining scandals not only included the salting of cores, but also unreliable proprietary sample preparation and assay methods, mis-representations of visual field estimates as drilling results and ‘overly optimistic’ geological reports. This paper reports on initiatives taken in the wake of these scandals and prompted by the Mining Standards Task Force (TSE/OSC 1999). For regulators, mandated to increase investor confidence in Canada’s leading role within the global mining industry, efforts focused first and foremost upon identifying and removing sources of error and wilfulness within the production and circulation of scientific knowledge claims. A common goal cross-cutting these initiatives was ‘a faithful representation of nature’ (Daston and Galison 2010), however, as the paper argues, this was manifest in an assemblage of practices governed by distinct and rival regulative visions of science and the making of markets in claims about ‘nature’. These ‘practices of fidelity’, it is argued, can be consequential in shaping the spatial and temporal dynamics of the marketization of nature.

Cancer dormancy: a model of early dissemination and late cancer recurrence

Cancer dormancy is a stage in tumor progression in which residual disease remains occult and asymptomatic for a prolonged period of time. Dormant tumor cells can be present as one of the earliest stages in tumor development, as well as a stage in micrometastases, and/or minimal residual disease left after an apparently successful treatment of the primary tumor. The general mechanisms that regulate the transition of disseminated tumor cells that have lain dormant into a proliferative state remain largely unknown. However, regulation of the growth from dormant tumor cells may be explained in part through the interaction of the tumor cell with its microenvironment, limitations in the blood supply, or an active immune system. An understanding of the regulatory machinery of these processes is essential for identifying early cancer biomarkers and could provide a rationale for the development of novel agents to target dormant tumor cells. This review focuses on the different signaling models responsible for early cancer dissemination and tumor recurrence that are involved in dormancy pathways.

The extracellular vesicles of the helminth pathogen, Fasciola hepatica: biogenesis pathways and cargo molecules involved in parasite pathogenesis.

Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterisation of the total secretome of this zoonotic parasite. Fasciola secretes at least two sub-populations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialised cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic datasets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular machinery required for EV biogenesis is constitutively expressed across the intra-mammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.

Parametric scans of HB and LS-RPA regimes employing Petawatt laser

By contrast to the Target Normal Sheath acceleration (TNSA) mechanism [1], Radiation Pressure Acceleration (RPA) is currently attracting a substantial amount of experimental [2,3] and theoretical [4-6] attention worldwide due to its superior scaling in terms of ion energy and laser-ion conversion efficiency. Employing Vulcan Petawatt lasers of the Rutherford Appleton Laboratory, UK, both the Hole-boring (HB) and the Light-Sail (LS) regimes of the RPA have been extensively explored. When the target thickness is of the order of hole-boring velocity times the laser pulse duration, highly collimated plasma jets of near solid density are ejected from the foil, lasting up to ns after the laser interaction. By changing the linear polarisation of the laser to circular, improved homogeneity in the jet's spatial density profile is achieved which suggests more uniform and sustained radiation pressure drive on target ions. By decreasing the target areal density or increasing irradiance on the target, the LS regime of the RPA is accessed where relatively high flux (~ 1012 particles/MeV/Sr) of ions are accelerated to ~ 10 MeV/nucleon energies in a narrow energy bandwidth. The ion energy scaling obtained from the parametric scans agrees well with theoretical estimation based on RPA mechanism and the narrow bandwidth feature in the ion spectra is studied by 2D particle-in-simulations.

Genotoxicity and cytotoxicity of Cr(VI) and Pb²+ in Pisum sativum

A toxicidade dos metais é uma problemática que envolve a saúde humana e o ambiente, sendo necessária uma vigilância constante e uma avaliação dos danos precisa e robusta. As plantas, como principal fonte alimentar e de produtos, são de vital importância à sociedade humana. Devido a serem seres sesseis, este grupo é um dos mais afectados por poluentes, tornandoos objectos de estudo extremamente interessantes. O objectivo desta tese foi avaliar os efeitos genotóxicos e citotóxicos do Cr(VI) e Pb2+ na espécie modelo Pisum sativum L. No capitulo I é introduzida a problemática da toxicidade de ambos os metais, com especial relevo nas plantas, bem como as abordagens mais actuais no estudo da geno e citotoxicidade. No capitulo II são apresentados os resultados dos estudos da genotoxicidade do Pb2+ (II-1) e Cr(VI) (II-2 e II-3), tendo sido realizados analises de dano ao DNA a vários níveis e alterações do ciclo celular (II-1 e II-2), bem como a detecção de instabilidade de microssatelites (II-1 e II-3), que é um indicador do estado funcional do mecanismo de reparação do DNA. O capítulo III aborda o efeito de stresses abióticos na capacidade fotossintética da espécie modelo. No capítulo III-1, realizou-se um estudo pioneiro de avaliação da aplicabilidade da citometria de fluxo no estudo da fotossíntese, mais concretamente no estado funcional e estrutural dos cloroplastos, quando expostos a um inibidor da fotossíntese (Paraquat). Os dados obtidos neste estudo encorajaram a aplicação da técnica nos capítulos III-2 e III-3, nos quais se analisaram os efeitos dos metais Pb2+ (III- 2) e Cr(VI) (III-3) na capacidade fotossintética de plantas expostas a este metal; em estudos que envolveram vários marcadores clássicos, para alem dos da citometria de fluxo. Finalmente, no capítulo IV são apresentadas as conclusões finais do trabalho, uma comparativa entre os efeitos e níveis de toxicidade dos dois metais em estudo e são apontadas algumas perspectivas para futuros estudos, levantadas pelos dados obtidos.

Theoretical and Experimental Foundations for the Greystar Project. Or application of NAA for remote detection

Dans un monde de détection et prospection minière, une multitude de techniques existent. Une des techniques les plus puissantes est l’activation par neutrons (NAA et PGAA). Toutefois, dans le cadre de la prospection minière, l’utilisation de cette technique nécessite du forage. La motivation du projet GREYSTAR est de permettre l’analyse élémentaire par activation en limitant l’impact environnemental. Les facteurs limitant sont l’activation d’un volume distant et la détection de la radiation émise par ce volume. Ce mémoire examine l’activation par neutrons thermiques et la détection de gammas provenant de la désexcitation des noyaux activés. Une approche expérimentale est présentée avec des simulations pour venir appuyer les données expérimentales. Il en résulte que le projet GREYSTAR tel que décrit dans ce mémoire est prometteur et que davantage de recherche est à prescrire. Les résultats initiaux indiquent que selon le prototype proposé, les limites de détections sont de l’ordre de 2-3 m dans un matériel semblable au granite. On conclut que d’un point de vue de prospection minière, il est intéressant de poursuivre la recherche. De plus, plusieurs autres applications dans les domaines militaire, civil et policier sont prometteuses.

Tool effects on hybrid laminates drilling

Fiber reinforced plastics are increasing their importance as one of the most interesting groups of material on account of their low weight, high strength, and stiffness. To obtain good quality holes, it is important to identify the type of material, ply stacking sequence, and fiber orientation. In this article, the drilling of quasi-isotropic hybrid carbon +glass/epoxy plates is analyzed. Two commercial drills and a special step drill are compared considering the thrust force and delamination extension. Results suggest that the proposed step drill can be a suitable option in laminate drilling.