A Stochastic Multiscale Model of Cardiac Thin Filament Activation Using Brownian-Langevin Dynamics.

We use Brownian-Langevin dynamics principles to derive a coarse-graining multiscale myofilament model that can describe the thin-filament activation process during contraction. The model links atomistic molecular simulations of protein-protein interactions in the thin-filament regulatory unit to sarcomere-level activation dynamics. We first calculate the molecular interaction energy between tropomyosin and actin surface using Brownian dynamics simulations. This energy profile is then generalized to account for the observed tropomyosin transitions between its regulatory stable states. The generalized energy landscape then served as a basis for developing a filament-scale model using Langevin dynamics. This integrated analysis, spanning molecular to thin-filament scales, is capable of tracking the events of the tropomyosin conformational changes as it moves over the actin surface. The tropomyosin coil with flexible overlap regions between adjacent tropomyosins is represented in the model as a system of coupled stochastic ordinary differential equations. The proposed multiscale approach provides a more detailed molecular connection between tropomyosin dynamics, the trompomyosin-actin interaction-energy landscape, and the generated force by the sarcomere

Amplitude equations for Rayleigh-Benard convective rolls far from threshold

An extension of the amplitude method is proposed. An iterative algorithm is developed to build an amplitude equation model that is shown to provide precise quantitative results even far from the linear instability threshold. The method is applied to the study of stationary Rayleigh-Benard thermoconvective rolls in the nonlinear regime. In particular, the generation of second and third spatial harmonics is analyzed. Comparison with experimental results and direct numerical calculations is also made and a very good agreement is found.Peer reviewe

Potential of marula (Sclerocarya birrea subsp. caffra) waste for the production of vinegar through surface and submerged fermentation

Although there is an abundance of indigenous fruits in South Africa, knowledge of their potential uses is mainly restricted to within communities. In this study, marula fruit-processing waste by-products (fruit pulp residue and skin) were used as substrates in surface culture and submerged fermentation methods to produce vinegar (acetic acid) using spontaneous and starter culture techniques. The study revealed the possibility of producing vinegar through both methods of fermentation, with yields of acetic acid ranging between 41 000 mg/L and 57 000 mg/L (surface culture method) and between 41 000 and 54 000 mg/L (submerged culture method). Furthermore, the physicochemical property analyses revealed marula vinegar to be a potential source of bioactive compounds (total phenolics 0.289–0.356 mg/L GAE and total flavonoids 0.146–0.153 mg/L CAE) which displayed a potent antiradical activity against DPPH•: 78.85% for surface culture and 73.03% submerged culture, respectively. The sensory panel recommended application of the vinegar in products such as salad dressing and mayonnaise. Finally, we have demonstrated that the surface culture method using the inoculation technique is more suitable for the production of high-quality vinegar, with possible consideration for commercialisation. Significance: • Marula fruit has high economic importance for South Africa, particularly for the Limpopo Province. • Marula waste can be a source of bioactive compounds, yet comparatively little is reported on the potential use of the waste to produce vinegar. • Self-development of communities through viable and easy to produce commodities from marula fruit needs to be implemented and prioritised in the Limpopo Province

Triggered crustal earthquake swarm across subduction segment boundary after the 2016 Pedernales, Ecuador megathrust earthquake

Megathrust ruptures and the ensuing postseismic deformation cause stress changes that may induce seismicity on upper plate crustal faults far from the coseismic rupture area. In this study, we analyze seismic swarms that occurred in the north Ecuador area of Esmeraldas, beginning two months after the 2016 M$_{w}$ 7.8 Pedernales, Ecuador megathrust earthquake. The Esmeraldas region is 70 km from the Pedernales rupture area in a separate segment of the subduction zone. We characterize the Esmeraldas sequence, relocating the events using manual arrival time picks and a local a-priori 3D velocity model. The earthquake locations from the Esmeraldas sequence outline an upper plate fault or shear zone. The sequence contains one major swarm and several smaller swarms. Moment tensor solutions of several events include normal and strike-slip motion and non-double-couple components. During the main swarm, earthquake hypocenters increase in distance from the first event over time, at a rate of a few hundred meters per day, consistent with fluid diffusion. Events with similar waveforms occur within the sequence, and a transient is seen in time series of nearby GPS stations concurrent with the seismicity. The events with similar waveforms and the transient in GPS time series suggest that slow aseismic slip took place along a crustal normal fault during the sequence. Coulomb stress calculations show a positive Coulomb stress change in the Esmeraldas region, consistent with seismicity being triggered by the Pedernales mainshock and large aftershocks. The characteristics of the seismicity indicate that postseismic deformation involving fluid flow and slow slip activated upper plate faults in the Esmeraldas area. These findings suggest the need for further investigation into the seismic hazard potential of shallow upper plate faults and the potential for megathrust earthquakes to trigger slow-slip and shallow seismicity across separate segments of subduction zones

A novel human skin chamber model to study wound infection ex vivo

Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum® and cultivated for 7 days in an air–liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (105 CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this timepoint, 1.8 × 108 CFU/g tissue of P. aeruginosa and 2 × 107 CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum® is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum® presents a convenient model and may help to standardize wound research