879 research outputs found

    miRNAs and cancer

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    Statistical analysis of the induced Basel 2006 earthquake sequence: introducing a probability-based monitoring approach for Enhanced Geothermal Systems

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    Geothermal energy is becoming an important clean energy source, however, the stimulation of a reservoir for an Enhanced Geothermal System (EGS) is associated with seismic risk due to induced seismicity. Seismicity occurring due to the water injection at depth have to be well recorded and monitored. To mitigate the seismic risk of a damaging event, an appropriate alarm system needs to be in place for each individual experiment. In recent experiments, the so-called traffic-light alarm system, based on public response, local magnitude and peak ground velocity, was used. We aim to improve the pre-defined alarm system by introducing a probability-based approach; we retrospectively model the ongoing seismicity in real time with multiple statistical forecast models and then translate the forecast to seismic hazard in terms of probabilities of exceeding a ground motion intensity level. One class of models accounts for the water injection rate, the main parameter that can be controlled by the operators during an experiment. By translating the models into time-varying probabilities of exceeding various intensity levels, we provide tools which are well understood by the decision makers and can be used to determine thresholds non-exceedance during a reservoir stimulation; this, however, remains an entrepreneurial or political decision of the responsible project coordinators. We introduce forecast models based on the data set of an EGS experiment in the city of Basel. Between 2006 December 2 and 8, approximately 11 500 m3 of water was injected into a 5-km-deep well at high pressures. A six-sensor borehole array, was installed by the company Geothermal Explorers Limited (GEL) at depths between 300 and 2700 m around the well to monitor the induced seismicity. The network recorded approximately 11 200 events during the injection phase, more than 3500 of which were located. With the traffic-light system, actions where implemented after an ML 2.7 event, the water injection was reduced and then stopped after another ML 2.5 event. A few hours later, an earthquake with ML 3.4, felt within the city, occurred, which led to bleed-off of the well. A risk study was later issued with the outcome that the experiment could not be resumed. We analyse the statistical features of the sequence and show that the sequence is well modelled with the Omori-Utsu law following the termination of water injection. Based on this model, the sequence will last 31+29/−14 years to reach the background level. We introduce statistical models based on Reasenberg and Jones and Epidemic Type Aftershock Sequence (ETAS) models, commonly used to model aftershock sequences. We compare and test different model setups to simulate the sequences, varying the number of fixed and free parameters. For one class of the ETAS models, we account for the flow rate at the injection borehole. We test the models against the observed data with standard likelihood tests and find the ETAS model accounting for the on flow rate to perform best. Such a model may in future serve as a valuable tool for designing probabilistic alarm systems for EGS experiment

    HighSTEPS. A high strain temperature pèressure and speed apparatus to study earthquake mechanics

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    We present a state of-the-art biaxial apparatus able to study both earthquake rupture nucleation and propagation at conditions typical of the seismogenic crust. The HighSTEPS, High Strain TEmperature Pressure Speed, apparatus simulates fault deformation in a wide range of slip velocities, i.e., from 10-5m/s to 0.25 m/s. Within this velocity range, it is possible to study, the rate-and-state friction, the fault dynamic weakening, and healing under unique boundary conditions, i.e., normal stress up to 100 MPa, confining pressure up to 100 MPa, pore fluid pressure up to 100 MPa and temperature up to 120 °C. The apparatus consists of a hydraulic system integrated with four linear motors. The hydraulic system allows for the application of normal stress, confining pressure and pore fluid pressure. The main peculiarity of this apparatus is the system of four linear motors that are mounted in series in order to apply shearing velocities up to 0.25 m/s, accelerations up to 10 m/s2 and shear stresses up to 200 MPa. Moreover, both experiments in sliding velocity control or shear stress control on the experimental faults are possible. Preliminary experiments on carbonate and silicate bearing rocks are coherent with the previous literature. The investigation of fault friction under a wide range of velocities, normal stresses, confining pressures and pore fluid pressures will provide insights into the mechanics of earthquakes and reduce the gap between natural and laboratory observations

    Interface Analysis of MOCVD Grown GeTe/Sb2Te3 and Ge-Rich Ge-Sb-Te/Sb2Te3 Core-Shell Nanowires

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    Controlling material thickness and element interdiffusion at the interface is crucial for many applications of core-shell nanowires. Herein, we report the thickness-controlled and conformal growth of a Sb2Te3 shell over GeTe and Ge-rich Ge-Sb-Te core nanowires synthesized via metal-organic chemical vapor deposition (MOCVD), catalyzed by the Vapor-Liquid-Solid (VLS) mechanism. The thickness of the Sb2Te3 shell could be adjusted by controlling the growth time without altering the nanowire morphology. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were employed to examine the surface morphology and the structure of the nanowires. The study aims to investigate the interdiffusion, intactness, as well as the oxidation state of the core-shell nanowires. Angle-resolved X-ray photoelectron spectroscopy (XPS) was applied to investigate the surface chemistry of the nanowires. No elemental interdiffusion between the GeTe, Ge-rich Ge-Sb-Te cores, and Sb2Te3 shell of the nanowires was revealed. Chemical bonding between the core and the shell was observed

    Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock

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    Background: In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed. Methods: From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes. Results: Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6–9] vs. 12d [IQR 9–16]; p = 0.002). No differences were seen in terms of other clinical outcomes. Conclusion: In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing

    The spliceosome as target for anticancer treatment

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    The spliceosome is a ribonucleoprotein complex involved in RNA splicing, that is, the removal of non-coding introns from precursor messenger RNA. (Alternative) Splicing events may play an essential role in tumourigenesis. The recent discovery that the spliceosome is a target for novel compounds with anticancer activity opens up new therapeutic avenues

    MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells

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    Background: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal. Methods: MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells. Results: MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death. Conclusion: These results highlight the importance of miR-193b in determining oesophageal cancer cell viability and demonstrate an enhancement of chemotoxicity that is independent of apoptosis induction

    High Conservatism in the Composition of Scent Gland Secretions in Cyphophthalmid Harvestmen: Evidence from Pettalidae

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    The scent gland secretion of Austropurcellia forsteri was analyzed by gas chromatography–mass spectrometry, providing the first description of the secretion chemistry in the cyphophthalmid family Pettalidae. The secretion contained a total of 21 compounds: About 60% of the whole secretion consisted of a series of saturated, mono-unsaturated and doubly unsaturated methylketones, from C11 to C15, with a cluster of saturated and mono-unsaturated C13-methylketones dominating. A second fraction included several naphthoquinones such as 1,4-naphthoquinone (ca. 20% of secretion), 6-methyl-1,4-naphthoquinone (ca. 17%), and minor amounts of chloronaphthoquinones (ca. 2%). When compared with scent gland compositions of other representatives of cyphophthalmids (e.g. from families Sironidae and Stylocellidae), a highly conservative chemistry of cyphophthalmid secretions is apparent, based on a restricted number of methylketones and naphthoquinones
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