9,226 research outputs found
A coarse graining approach to determine nucleic acid structures from small angle neutron scattering profiles in solution
We present a theoretical method to calculate the small angle neutron scattering profile of nucleic acid structures in solution. Our approach is sensitive to the sequence and the structure of the nucleic acid. In order to test our approach, we apply this method to the calculation of the experimental scattered intensity of the decamer d(CCAACGTTGG)(2) in H(2)O. This sequence was specifically chosen for this study as it is believed to adopt a canonical B-form structure in 0.3 M NaCl. We find that not only will our methodology reproduce the experimental scattered intensity for this sequence, but our method will also discriminate between B-, A- and Z-form DNA. By studying the scattering profile of this structure in 0.5 and 1.0 M NaCl, we are also able to identify tetraplex and other similar oligomers formation and to model the complex using the experimental scattering data in conjunction with our methodology
Temporal characteristics of oxygenation-sensitive MRI responses to visual activation in humans.
Hydrodynamic Fin Function of Brief Squid, Lolliguncula Brevis
Although the pulsed jet is often considered the foundation of a squid\u27s locomotive system, the lateral fins also probably play an important role in swimming, potentially providing thrust, lift and dynamic stability as needed. Fin morphology and movement vary greatly among squid species, but the locomotive role of the fins is not well understood. To begin to elucidate the locomotive role of the fins in squids, fin hydrodynamics were studied in the brief squid Lolliguncula brevis, a species that exhibits a wide range of fin movements depending on swimming speed. Individual squid were trained to swim in both the arms-first and tail-first orientations against currents in a water tunnel seeded with light-reflective particles. Particle-laden water around the fins was illuminated with lasers and videotaped so that flow dynamics around the fins could be analyzed using digital particle image velocimetry (DPIV). Time-averaged forces generated by the fin were quantified from vorticity fields of the fin wake. During the low swimming speeds considered in this study [\u3c2.5 dorsal mantle lengths (DML) per second], L. brevis exhibited four unique fin wake patterns, each with distinctive vortical structures: (1) fin mode I, in which one vortex is shed with each downstroke, generally occurring at low speeds; (2) fin mode II, an undulatory mode in which a continuous linked chain of vortices is produced; (3) fin mode III, in which one vortex is shed with each downstroke and upstroke, and; (4) fin mode IV, in which a discontinuous chain of linked double vortex structures is produced. All modes were detected during tail-first swimming but only fin modes II and III were observed during arms-first swimming. The fins produced horizontal and vertical forces of varying degrees depending on stroke phase, swimming speed, and swimming orientation. During tail-first swimming, the fins functioned primarily as stabilizers at low speeds before shifting to propulsors as speed increased, all while generating net lift. During arms-first swimming, the fins primarily provided lift with thrust production playing a reduced role. These results demonstrate the lateral fins are an integral component of the complex locomotive system of L. brevis, producing lift and thrust forces through different locomotive modes
Functional mri of human brain activation combining high spatial and temporal resolution by a cine flash technique
Microscale Discrete Element Method Simulation of the Carbon Black Aggregate Fracture Behavior in a Simple Shear Flow
The shear stress induced breaking behavior of carbon black (CB) aggregates during the manufacturing process of Li‐ion batteries is investigated via microscale discrete element method (DEM) simulations. The relevant range of shear stress is chosen according to a planetary mixer and cathode slurries with high solid content. Aggregates of different sizes and shapes are modeled using a self‐written algorithm based on the tunable dimension method. Then, suitable models are chosen for representing the solid bridges between the primary particles of the CB aggregates and relevant fluid forces. The results show a correlation between aggregate size and critical shear stress which is required to initiate aggregate fracturing. Furthermore, a change in aggregate shape is linked to applied stress and initial aggregate size and shape. Hence, a recommendation for an efficient disintegration of CB aggregates during the mixing process is made
CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome
AIMS Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor under development for reducing cardiovascular events in patients with high risk vascular disease. CETP inhibitors are likely to be utilized as ‘add-on’ therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug–drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated. METHODS The DDI potential of evacetrapib was investigated in vitro, followed by predictions to determine clinical relevance. Potential DDIs with possible clinical implications were then investigated in the clinic. RESULTS In vitro, evacetrapib inhibited all of the major CYPs, with inhibition constants (Ki) ranging from 0.57 μM (CYP2C9) to 7.6 μM (CYP2C19). Evacetrapib was a time-dependent inhibitor and inducer of CYP3A. The effects of evacetrapib on CYP3A and CYP2C9 were assessed in a phase 1 study using midazolam and tolbutamide as probe substrates, respectively. After 14 days of daily dosing with evacetrapib (100 or 300 mg), midazolam exposures (AUC) changed by factors (95% CI) of 1.19 (1.06, 1.33) and 1.44 (1.28, 1.62), respectively. Tolbutamide exposures (AUC) changed by factors of 0.85 (0.77, 0.94) and 1.06 (0.95, 1.18), respectively. In a phase 2 study, evacetrapib 100 mg had minimal impact on AUC of co-administered simvastatin vs. simvastatin alone with a ratio of 1.25 (1.03, 1.53) at steady-state, with no differences in reported hepatic or muscular adverse events. CONCLUSIONS Taken together, the extent of CYP-mediated DDI with the potential clinical dose of evacetrapib is weak and clinically important DDIs are not expected to occur in patients taking concomitant medications.Ellen A. Cannady, Jeffrey G. Suico, Ming-Dauh Wang, Stuart Friedrich, Jessica R. F. Rehmel, Stephen J. Nicholls, Kathryn A. Kruege
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