Averaging-based approach to toughness homogenisation for radial hydraulic fracture

The homogenisation of the fracture toughness is considered in the context of a propagating hydraulic fracture. The radial (penny-shape) model is utilized, in order to incorporate the impact of the viscosity-toughness regime transition over time. A homogenisation strategy based upon temporal-averaging is investigated. This approach incorporates the instantaneous fracture velocity, meaning that it should remain effective in the case of step-wise crack advancement. The effectiveness of the approach is demonstrated for periodic toughness distributions, including those which are unbalanced, utilizing a highly accurate solver.Comment: 39 pages, 22 figure

Seismic anisotropy in deforming halite:Evidence from the Mahogany salt body

We present unambiguous evidence that the Mahogany salt body, located in the Northern part of the Gulf of Mexico, is seismically anisotropic. Evidence of anisotropy comes from shear wave splitting data obtained from a vertical seismic profile VSP. The data set consists of 48 vertically aligned receivers in a borehole drilled through the salt body. Splitting analysis is performed on shear wave phases that are converted from compressional waves at the top and bottom of the salt body. The phase converted at the top of the salt layer shows a clear signature of seismic anisotropy, while the phase at the base of the salt layer shows negligible splitting. We investigate the possibility of rock salt halite LPO as a cause of the observed anisotropy. A finite element geomechanical salt deformation model of the Mahogany salt body is developed, where deformation history is used as an input to the texture plasticity simulation program VPSC. Assuming a halite salt body, a full elasticity model is then calculated and used to create a synthetic VSP splitting data set. The comparison between the synthetic and real VSP data set shows that LPO of rock salt can explain the observed anisotropy remarkably well. This is the strongest evidence to date of seismic anisotropy in a deforming salt structure. Furthermore, for the first time, we are able to demonstrate clear evidence that deforming halite is the most likely cause of this anisotropy, combining data set analysis and synthetic full wave form modelling based on calculated rock salt elasticities. Neglecting anisotropy in seismic processing in salt settings could lead to potential imaging errors, for example the deformation models show an averaged delta parameter of δ=-0.06, which would lead in a zero offset reflection setting to a depth mismatch of 6.2 per cent. Our work also show how observations of salt anisotropy can be used to probe characteristics of salt deformation

Zur Lösung ebener und räumlicher, geometrisch nichtlinearer Aufgaben mit Hilfe der Methode der finiten Elemente bei elastisch-plastischen Materialgesetzen mit kinematisch-isotroper Verfestigung

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Characterization of LINE-1 Ribonucleoprotein Particles

The average human genome contains a small cohort of active L1 retrotransposons that encode two proteins (ORF1p and ORF2p) required for their mobility (i.e., retrotransposition). Prior studies demonstrated that human ORF1p, L1 RNA, and an ORF2p-encoded reverse transcriptase activity are present in ribonucleoprotein (RNP) complexes. However, the inability to physically detect ORF2p from engineered human L1 constructs has remained a technical challenge in the field. Here, we have employed an epitope/RNA tagging strategy with engineered human L1 retrotransposons to identify ORF1p, ORF2p, and L1 RNA in a RNP complex. We next used this system to assess how mutations in ORF1p and/or ORF2p impact RNP formation. Importantly, we demonstrate that mutations in the coiled-coil domain and RNA recognition motif of ORF1p, as well as the cysteine-rich domain of ORF2p, reduce the levels of ORF1p and/or ORF2p in L1 RNPs. Finally, we used this tagging strategy to localize the L1–encoded proteins and L1 RNA to cytoplasmic foci that often were associated with stress granules. Thus, we conclude that a precise interplay among ORF1p, ORF2p, and L1 RNA is critical for L1 RNP assembly, function, and L1 retrotransposition

Plánování investic pro MHD v Ostravě, možnosti financování a zhodnocení efektivnosti jejich pořízení

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Ekonomická fakulta. Katedra (154) financ

Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial.

Comment in New kids on the block--step by step to an ideal HCV therapy. [Lancet. 2015]International audienceThere is a high medical need for an interferon-free, all-oral, short-duration therapy for hepatitis C virus (HCV) that is highly effective across diverse patient populations, including patients with cirrhosis or previous null response to pegylated interferon (peginterferon) plus ribavirin (PR-null responders). We aimed to assess the efficacy, safety, and effective treatment duration of grazoprevir (an HCV NS3/4A protease inhibitor) combined with elbasvir (an HCV NS5A inhibitor) with or without ribavirin in patients with HCV genotype 1 infection with baseline characteristics of poor response. The C-WORTHY trial is a randomised, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin; here we report findings for two cohorts of previously untreated patients with cirrhosis (cohort 1) and those with previous PR-null response with or without cirrhosis (cohort 2) enrolled in part B of the study. Eligible patients were adults aged 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10 000 IU/mL or higher in peripheral blood. We randomly assigned patients to receive grazoprevir (100 mg daily) and elbasvir (50 mg daily) with or without ribavirin for 12 or 18 weeks. Randomisation was done centrally with an interactive voice response system; patients and study investigators were masked to treatment duration up to week 12 but not to treatment allocation. The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after end of treatment (SVR12), assessed by COBAS TaqMan version 2.0. This study is registered with ClinicalTrials.gov, number NCT01717326. We describe findings for 253 patients enrolled in cohort 1 (n=123) or cohort 2 (n=130). In cohort 1, we randomly assigned 60 patients to the 12-week regimen (31 with ribavirin and 29 with no ribavirin) and 63 to the 18-week regimen (32 with ribavirin and 31 with no ribavirin); in cohort 2, we randomly assigned 65 patients to the 12-week regimen (32 with ribavirin and 33 with no ribavirin) and 65 to the 18-week regimen (33 with ribavirin and 32 with no ribavirin. High SVR12 rates were achieved irrespective of the use of ribavirin or extension of the treatment duration from 12 to 18 weeks; SVR12 rates ranged from 90% (95% CI 74-98; 28/31; cohort 1, 12 weeks, ribavirin-containing) to 100% (95% CI 89-100; 33/33; cohort 2, 18 weeks, ribavirin-containing). Among patients treated for 12 weeks with grazoprevir plus elbasvir without ribavirin, 97% (95% CI 82-100, 28/29) of patients in cohort 1 and 91% (76-98, 30/33) of patients in cohort 2 achieved SVR12. Adverse events reported in more than 10% of patients were fatigue (66 patients, 26% [95% CI 21-32]), headache (58 patients, 23% [95% CI 18-29]), and asthenia (35 patients, 14% [95% CI 10-19]). Treatment with grazoprevir plus elbasvir, both with and without ribavirin and for both 12 and 18 weeks' treatment duration, showed high rates of efficacy in previously untreated patients with cirrhosis and previous PR-null responders with and without cirrhosis. These results support the phase 3 development of grazoprevir plus elbasvir

Efficacy and safety of MK-5172 and MK-8742 +/- ribavirin in hepatitis C genotype 1 infected patients with cirrhosis or previous null response: Final results of the C-WORTHY Study (Parts A and B)

International audienc