Finite strains fully coupled analysis of a horizontal wellbore drilled through a porous rock formation

Wellbore instability, in particular in deep perforations, continues to be one of the major problem in the oil and gas industry, that can dramatically increase production costs. Eventual instabilities may be prevented supporting temporarily the wellbore with mud circulation. If instability may occur, the value of the mud pressure needs to be sufficiently high to prevent compressional failure, but it should also be lower than a critical value that would cause tensile failure and unintentional hydraulic fracturing. Predicting faithfully the stress distribution around a borehole, and moreover the yielding and failure zones, is a challenging but fundamental task, essential to estimate the correct mud pressure and hence to prevent instabilities and sand production. This study focuses on quantifying the pressure distribution, stress field and plastic zones around a horizontal borehole drilled at great depth through a highly porous rock formation. The perforation of a wellbore in a saturated porous material is a coupled problem, which involves deformations of the solid phase and simultaneous diffusion of the fluid phase. A fully coupled finite element method is adopted, considering both material non linearity (elastoplasticity) and geometric nonlinearity (finite deformations) in the solid matrix, resulting in a so called u−p formulation. The variation of porosity and permeability, as consequence of the finite deformations of the solid matrix, is taken into account. The model adopts an elastoplastic constitutive law characterized by two yield surfaces, that is able to capture the dilatant and compactant plastic mechanism. The simulations investigate the quasi-static transient phenomenon associated with the perforation, until the steady state condition is reached. The model describes the evolution of the stress and pressure distribution, and moreover the propagation of the plastic zones around the borehole. The work demonstrates the capability of the finite deformations coupled approach to simulate the whole process, giving an instrument to determine the stability and sand production of the wellbore

Aggregate behaviour in concrete materials under high temperature conditions

Concrete under high temperature conditions is a topic of wide interest for applications in several engineering fields, from nuclear to civil as well as building engineering

Numerical modelling of ellipsoidal inclusions

Within the framework of numerical algorithms for the threedimensional random packing of granular materials this work presents an innovative formulation for polydispersed ellipsoidal particles, including an overlapping detection algorithm for an optimized simulation of the mesostructure of geomaterials, particularly concrete. Granular composite cement-based materials can be so reconstructed with adequate precision in terms of grain size distribution. Specifically, the algorithm performance towards the assumed inclusion shape (ellipsoidal or spheric) and degree of regularity (round or irregular) is here discussed. Examples on real grading curves prove that this approach is effective. The advantages of the proposed method for computational mechanics purposes are also disclosed when properly interfaced with visualization CAD (Computer Aided Design) tools

Investigation of stress-strain behaviour in concrete materials through the aid of 3D advanced measurement techniques

This work deals with the investigation of the mechanical behaviour of cementitious materials, following a mesoscopic approach where aggregates, grains and cement paste are explicitly represented, and the strict comparison between the numerical results and the experimental results from uniaxial tests is carried out. For this purpose, solid models are created with the support of advanced techniques of measurement and detection, such as laser scanners or computer tomography (CT). The 3D laser- scanning technique in fact allows to acquire the exact shape of the grains added to the concrete mix design while, through the adoption of an ad-hoc random distribution algorithm, a realistic disposition of the inclusions is guaranteed. The industrial CT instead, is able to reproduce exactly the tested specimens; the geometry of the inclusions and their placement. Once reconstructed realistic geometries for the models, the mechanical behaviour of concrete under uniaxial compression tests is numerically studied. A specific constitutive behaviour is assigned to each component; an elasto-plastic law with damage is assumed for the cement matrix while the aggregates are conceived to behave elastically. The implemented damage-plasticity model consists in the combination of the non-associated plasticity model by Men\ue9trey-Willam, where the yield surface is described in function of the second and the third invariant of the deviatoric stress tensor and the scalar isotropic damage model by Mazars. Comparisons between numerical and experimental results fairly prove the correctness of the suggested approach

Nonlinear Modelling, Design, and Test of Steel Blast-Resistant Doors

The nonlinear dynamic response for steel blast-resistant doors is here described, referring to an innovative experience at both national and international level requiring an ad hoc design and specific numerical simulations. The elements capability to sustain thermal loads due to fire hazards is additionally accounted for. The study has been conducted to define and characterize the nonlinear behaviour of a large number of doors, with the objective of sustaining dynamic loads from explosive hazards of fixed magnitude, as well as variable design and clearing times. The local overcome of the material strength limit (with correspondent plastic response) and possible formation of plastic hinges has been critically discussed. Numerical models have allowed for refining first design sketches and subsequently understanding the real thermomechanical behaviour for the investigated elements. Some experimental tests have been additionally performed, verifying the correctness of the already available numerical results, validating the adopted procedures, and correspondingly guaranteeing the doors' structural efficiency even under dynamic loads higher than design ones

Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells

The final published version can be found here: http://dx.doi.org/10.1073/pnas.141316511

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

A promyelocytic leukemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma

Purpose. Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes such as MYCN and ALK and loss of tumour suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations. Experimental design. Neuroblastoma cell lines were used for assessment of tumour growth in vivo and in vitro. Protein expression in tissues and cells was assessed using immunofluorescence and immunohistochemistry. The association of PML expression with neuroblastoma outcome and relapse was calculated using log-rank and Mann-Whitney tests, respectively. Gene expression was assessed using chip microarrays. Results: PML is detected in the developing and adult sympathetic nervous system, whereas it is not expressed or low in metastatic neuroblastoma tumours. Reduced PML expression in patients with low-risk cancers - i.e. localized and negative for the MYCN protooncogene - is strongly associated with tumour recurrence. PML-I, but not PML-IV, isoform suppresses angiogenesis via upregulation of thrombospondin-2 (TSP-2), a key inhibitor of angiogenesis. Finally, PML-I and TSP-2 expression inversely correlates with tumour angiogenesis and recurrence in localized neuroblastomas. Dvorkina et al. A promyelocytic leukaemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma 3 Conclusions: Our work reveals a novel PML-I-TSP2 axis for regulation of angiogenesis and cancer relapse, which could be used to identify patients with low-risk, localized tumours that might benefit from chemotherapy

Immunohistochemical expression of promyelocytic leukemia body in soft tissue sarcomas

<p>Abstract</p> <p>Background</p> <p>The function of promyelocytic leukemia (PML) bodies is not well known but plays an important role in controlling cell proliferation, apoptosis and senescence. This study was undertaken to analyze the clinical significance of PML body expression in primary tumor samples from malignant fibrous histiocytoma (MFH) and liposarcoma patients.</p> <p>Methods</p> <p>We studied MFH and liposarcoma samples from 55 patients for PML bodies. Fluorescent immunostaining of PML bodies was performed in the paraffin-embedded tumor sections.</p> <p>Results</p> <p>PML body immunostaining was identified in 63.9% of MFH and 63.2% of liposarcoma samples. PML body expression rates of all sarcoma cells were 1.5 ± 1.8% (range: 0–7.0) in MFH and 1.3 ± 1.4% (0–5.2) in liposarcoma samples. PML body expression (p = 0.0053) and a high rate of PML body expression (p = 0.0012) were significantly greater prognostic risk factors for death than the other clinical factors in MFH patients. All liposarcoma patients without expression of PML were disease free at the end of the study.</p> <p>Conclusion</p> <p>Our study suggests that the presence of PML bodies may indicate a poor prognosis for MFH and liposarcoma patients.</p