Shale formations, due to the presence of laminations and weak planes, exhibit directional strength characteristics. In most conventional wellbore stability analyses, rock formations are typically ...assumed to have isotropic strength. This may cause erroneous results in anisotropic formations such as shales which show strength variations with changing loading directions with respect to the plane of weakness. Therefore a more complex wellbore stability model is required. We have developed such a model in which the anisotropic rock strength characteristic is incorporated. Applying this model to two case studies shows that shear failures occur either along or across the bedding planes depending on the relative orientation between the wellbore trajectories and the bedding planes. Additionally, the extent of failure region around the wellbore and the safe mud weights are significantly affected by the wellbore orientation with respect to the directions of bedding plane and in-situ stress field.
► Developed is a wellbore stability model in which anisotropic strength and two shear failure modes are considered. ► Wellbore failure depends on the relative orientation between well paths and weak planes. ► Safe mud weight also depends on their relative orientation. ► Generally an up-dip drilling is more stable than other drilling directions.
At great depths, where borehole-based field stress measurements such as hydraulic fracturing are challenging due to difficult downhole conditions or prohibitive costs, in situ stresses can be ...indirectly estimated using wellbore failures such as borehole breakouts and/or drilling-induced tensile failures detected by an image log. As part of such efforts, a statistical method has been developed in which borehole breakouts detected on an image log are used for this purpose (Song et al. in Proceedings on the 7th international symposium on in situ rock stress,
2016
; Song and Chang in J Geophys Res Solid Earth 122:4033–4052,
2017
). The method employs a grid-searching algorithm in which the least and maximum horizontal principal stresses (
S
h
and
S
H
) are varied, and the corresponding simulated depth-related breakout width distribution as a function of the breakout angle (
θ
B
= 90° − half of breakout width) is compared to that observed along the borehole to determine a set of
S
h
and
S
H
having the lowest misfit between them. An important advantage of the method is that
S
h
and
S
H
can be estimated simultaneously in vertical wells. To validate the statistical approach, the method is applied to a vertical hole where a set of field hydraulic fracturing tests have been carried out. The stress estimations using the proposed method were found to be in good agreement with the results interpreted from the hydraulic fracturing test measurements.
Breakouts observed in a vertical borehole (C0002A) drilled through two major tectonic sedimentary formations consisting of forearc basin (upper) and accretionary prism (lower) sediments in the Nankai ...accretionary wedge, Japan, exhibit distinctive geometric features in respective formations. Breakouts in the lower accretionary prism sediments are markedly wider than those in the forearc basin sediments, and breakout azimuths in the two units are horizontally rotated relative to one another. Breakout azimuths are widely used as a proxy for the determination of principal stress directions. However, strength anisotropies related to the presence of bedding planes may affect both breakout azimuths and widths, which can result in misleading in situ stress interpretations. While thinly bedded mudstones are the dominant lithology in both the forearc basin and accretionary prism sediments, bedding planes in the accretionary prism sediments are relatively steeper than those in the forearc basin sediments, with possible implications for breakout geometry and interpretations of principal stress directions. To investigate the effects of bedding planes on breakout geometry (azimuth and width), we conducted borehole wall failure analyses using a weak-plane failure model that incorporates material strength anisotropies. The model results show that breakout widths and orientations are strongly affected by steeply dipping (>40°) bedding planes in cases where dip directions are unaligned with the principal stress orientation. Our theoretical results suggest that variations in breakout azimuths in the C0002A site may be associated with bedding plane related strength anisotropy, and not associated with the rotation of stress field. That is, stress orientation is consistent throughout the borehole (down to the bottom-hole depth of 1495 m below sea floor). In addition, disregarding the effects of bedding planes tends to yield an overestimation of in situ stress magnitude.
•We model borehole breakouts considering anisotropic rock strength due to beddings.•Strength anisotropy affects significantly on breakout geometry as bedding is steep.•Ignoring anisotropy tends to yield an overestimation of stress magnitude.
To estimate critical pore pressure perturbation (CPP) for evaluating the reactivation potential of faults existing within a pilot-scale offshore CO2 storage site, we used a semi-analytical solution ...in which poroelastic stressing caused by subsurface fluid injection was taken into account. CPP is defined as the difference between the initial reservoir pressure and the pressure in response to CO2 injection that results in the reactivation of a fault. Estimating the critical threshold pressure requires information about the fault configuration and friction coefficient, the orientation and magnitude of in-situ stresses, and the reservoir rock properties. The three-dimensional geometry of the faults was mapped by interpreting the seismic data obtained from the site. The friction coefficient was measured by running a set of direct shear tests on natural fault gouges obtained from a fault near the site. The pre-injection in-situ stress field was characterized by integrating data from core measurements on samples retrieved from an exploration borehole drilled at the pilot site, and from well logs and well tests carried out in neighboring boreholes. In-situ stress changes in response to CO2 injection were incorporated into the fault reactivation analysis that was performed using two friction coefficients μ=0.25 (lower bound) and μ=0.6 (upper bound). The results showed that CPP was ~3MPa for μ=0.25 at the WF2 and EF3 faults, and ~10MPa for μ=0.6 at the EF3 fault. However, the upper bound was reduced to a threshold pressure of ~6MPa, above which horizontal hydraulic fracturing would occur in the reservoir. Therefore, the pressure increase allowed at the site ranged from 3MPa to 6MPa.
•A semi-analytical solution has developed to evaluate fault reactivation potential.•Faults oriented at a more acute angle to the SH direction are more prone to slip.•Well-defined fault geometry is critical for an accurate analysis of fault slip.
Aristolochic acid (AA), a natural product of Aristolochia plants found in herbal remedies and health supplements, is a group 1 carcinogen that can cause nephrotoxicity and upper urinary tract ...urothelial cell carcinoma (UTUC). Whole-genome and exome analysis of nine AA-associated UTUCs revealed a strikingly high somatic mutation rate (150 mutations/Mb), exceeding smoking-associated lung cancer (8 mutations/Mb) and ultraviolet radiation-associated melanoma (111 mutations/Mb). The AA-UTUC mutational signature was characterized by A:T to T:A transversions at the sequence motif AC|TAGG, located primarily on nontranscribed strands. AA-induced mutations were also significantly enriched at splice sites, suggesting a role for splice-site mutations in UTUC pathogenesis. RNA sequencing of AA-UTUC confirmed a general up-regulation of nonsense-mediated decay machinery components and aberrant splicing events associated with splice-site mutations. We observed a high frequency of somatic mutations in chromatin modifiers, particularly KDM6A, in AA-UTUC, demonstrated the sufficiency of AA to induce renal dysplasia in mice, and reproduced the AA mutational signature in experimentally treated human renal tubular cells. Finally, exploring other malignancies that were not known to be associated with AA, we screened 93 hepatocellular carcinoma genomes/exomes and identified AA-like mutational signatures in 11. Our study highlights an unusual genome-wide AA mutational signature and the potential use of mutation signatures as "molecular fingerprints" for interrogating high-throughput cancer genome data to infer previous carcinogen exposures.
Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene ...expression through H3K27 methylation. In urothelial bladder carcinoma,
(a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of
mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in
-mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in
-null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that
-null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in
-null cell lines. EZH2 inhibition delayed tumor onset in
-null cells and caused regression of
-null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of
, which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2.
Background
Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients ...diagnosed with MPN in developing countries is still undetermined.
Materials and methods
The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that.
Results
The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (
p
= 0.0285) and MPN-U (
p
= 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age hazard ratio (HR) 1.055, 95% CI 1.031; 1.064, reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945,
p
= 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217,
p
= 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503,
p
= 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701,
p
= 0.0335) at increased risk for worse mortality outcomes.
Conclusion
Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.
This dissertation addresses the mechanical stability of a borehole from theoretical, numerical, and experimental perspectives. The first two aspects are essentially concerned with the development of ...wellbore stability design codes. The experimental effort emphasized hydraulic fracturing of inclined boreholes in large cubical specimens. The wellbore stability codes were developed for the most general case where the borehole, in-situ stress, and rock property coordinate frames are totally independent of each other. The design codes enable the selection of the most optimum borehole orientation and wellbore fluid gradient. It is also useful in conducting sensitivity studies, particularly when data is scanty. A remarkable finding by exercising such codes was that borehole stability is strongly dependent on the formation and in-situ stress anisotropies, a contradiction to the industry thinking. An axisymmetric, plane strain, nonlinear formulation incorporating stress induced cylindrical anisotropy was also established. The nonlinear model was numerically solved using the 'shooting' technique. This 'semi-analytical' approach is very versatile as it enabled most expressions describing the evolutions of elastic moduli with stresses to be prescribed. Compared to the linear isotropic solution, the nonlinear anisotropic model predicted the value of the tangential stress at or near the borehole to be lower; the amount of reduction increased with the increasing degree of anisotropy. Also, failure analyses suggested that, for certain parameter combinations, failure can initiate inside the material instead of at the borehole wall as predicted by the linear elastic theory. Hydraulic fracturing of cement blocks was carried out in a polyaxial loading cell where six flatjacks were used to completely simulate the in-situ stresses. Close agreements between the theoretical and experimental fracture initiation pressure for some borehole configurations, coupled with the observed tensile failure modes, suggested that the linear elastic theory is applicable for predicting fracture initiation in this highly brittle material. These observations, besides resolving the controversy on failure modes during hydraulic fracturing of inclined boreholes, disqualify the present notion that linear elastic theory predictions are conservative.
