154 research outputs found

    3D finite element electrical model of larval zebrafish ECG signals

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    Assessment of heart function in zebrafish larvae using electrocardiography (ECG) is a potentially useful tool in developing cardiac treatments and the assessment of drug therapies. In order to better understand how a measured ECG waveform is related to the structure of the heart, its position within the larva and the position of the electrodes, a 3D model of a 3 days post fertilisation (dpf) larval zebrafish was developed to simulate cardiac electrical activity and investigate the voltage distribution throughout the body. The geometry consisted of two main components; the zebrafish body was modelled as a homogeneous volume, while the heart was split into five distinct regions (sinoatrial region, atrial wall, atrioventricular band, ventricular wall and heart chambers). Similarly, the electrical model consisted of two parts with the body described by Laplace’s equation and the heart using a bidomain ionic model based upon the Fitzhugh-Nagumo equations. Each region of the heart was differentiated by action potential (AP) parameters and activation wave conduction velocities, which were fitted and scaled based on previously published experimental results. ECG measurements in vivo at different electrode recording positions were then compared to the model results. The model was able to simulate action potentials, wave propagation and all the major features (P wave, R wave, T wave) of the ECG, as well as polarity of the peaks observed at each position. This model was based upon our current understanding of the structure of the normal zebrafish larval heart. Further development would enable us to incorporate features associated with the diseased heart and hence assist in the interpretation of larval zebrafish ECGs in these conditions

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    Reliability assessment of automotive components under fatigue using numerical simulation and accelerated testing

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    In this paper, a Stochastic Response Surface (SRS) approach based on Polynomial Chaos Expansion (PCE) is used to conduct reliability analysis of automotive components subjected to fatigue loading. The PCE coefficients have been computed by regression analysis based on a quasi-random experimental design. In addition, an efficient truncation technique, namely low-rank index sets, has been used to reduce the number of unknown coefficients to be estimated, and consequently to reduce the number of finite element model calls required for the construction of the PCE. Once the PCE is obtained, the probability of failure for a target fatigue life is estimated by applying Monte-Carlo simulations. At the same time, fatigue accelerated testing are conducted on full scale automotive component to obtain experimental predictions of the structural reliability. The estimates of the probability of failure are in good agreement with those obtained by numerical computations based on PCE and Monte-Carlo simulations

    Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors

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    In patients with the rare adult-type granulosa cell tumor tumor locations were cultured. On each cell line, 10 mono-(aGCT), surgery is the primary treatment for both primary and therapies and 17 combinations of drugs were tested. Carboplatin/ recurrent disease. In cases of inoperable disease, systematic gemcitabine showed efficacy and synergy in almost all patient-therapy is administered, but variable response rates and drug derived cell lines. Synergy could not be detected in the regular resistance complicate predicting the most effective therapy. Drug carboplatin/paclitaxel and carboplatin/etoposide combinations. screen testing on patient-derived cell lines may offer a solution. Experimental combinations alpelisib/fulvestrant and alpelisib/ In a national prospective study on aGCT, fresh tissue was cul- gemcitabine showed efficacy of more than 75%. Drug screens on tured into 2D cell lines, testing 27 clinical and experimental patient-derived tumor cell lines reflect the reality of the variable drugs. Dose–response curves and synergy were calculated using response of systemic therapy in patients with aGCT. In future GraphPad Prism and CompuSyn software. We established research, this technique may be used to personalize the systemic 34 patient-derived cell lines from tissue of 20 patients with aGCT. treatment of patients with aGCT in a clinical study. The good Of these, seven patients had a primary diagnosis of aGCT and response to carboplatin/gemcitabine in our patient-derived cell 13 patients had recurrent disease. In eight patients, multiple lines can then be confirmed in a clinical setting.</p

    Intragenic suppressors of temperature-sensitive rne mutations lead to the dissociation of RNase E activity on mRNA and tRNA substrates in Escherichia coli

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    RNase E of Escherichia coli is an essential endoribonuclease that is involved in many aspects of RNA metabolism. Point mutations in the S1 RNA-binding domain of RNase E (rne-1 and rne-3071) lead to temperature-sensitive growth along with defects in 5S rRNA processing, mRNA decay and tRNA maturation. However, it is not clear whether RNase E acts similarly on all kinds of RNA substrates. Here we report the isolation and characterization of three independent intragenic second-site suppressors of the rne-1 and rne-3071 alleles that demonstrate for the first time the dissociation of the in vivo activity of RNase E on mRNA versus tRNA and rRNA substrates. Specifically, tRNA maturation and 9S rRNA processing were restored to wild-type levels in each of the three suppressor mutants (rne-1/172, rne-1/186 and rne-1/187), while mRNA decay and autoregulation of RNase E protein levels remained as defective as in the rne-1 single mutant. Each single amino acid substitution (Gly→Ala at amino acid 172; Phe → Cys at amino acid 186 and Arg → Leu at amino acid 187) mapped within the 5′ sensor region of the RNase E protein. Molecular models of RNase E suggest how suppression may occur

    The Science Performance of JWST as Characterized in Commissioning

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    This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies
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