Controlling Protein Crystallization by Free Energy Guided Design of Interactions at Crystal Contacts

Protein crystallization can function as an effective method for protein purification or formulation. Such an application requires a comprehensive understanding of the intermolecular protein–protein interactions that drive and stabilize protein crystal formation to ensure a reproducible process. Using alcohol dehydrogenase from Lactobacillus brevis (LbADH) as a model system, we probed in our combined experimental and computational study the effect of residue substitutions at the protein crystal contacts on the crystallizability and the contact stability. Increased or decreased contact stability was calculated using molecular dynamics (MD) free energy simulations and showed excellent qualitative correlation with experimentally determined increased or decreased crystallizability. The MD simulations allowed us to trace back the changes to their physical origins at the atomic level. Engineered charge–charge interactions as well as engineered hydrophobic effects could be characterized and were found to improve crystallizability. For example, the simulations revealed a redesigning of a water mediated electrostatic interaction (“wet contact”) into a water depleted hydrophobic effect (“dry contact”) and the optimization of a weak hydrogen bonding contact towards a strong one. These findings explained the experimentally found improved crystallizability. Our study emphasizes that it is difficult to derive simple rules for engineering crystallizability but that free energy simulations could be a very useful tool for understanding the contribution of crystal contacts for stability and furthermore could help guide protein engineering strategies to enhance crystallization for technical purposes.

A Probabilistic Approach for Contact Stability and Contact Safety Analysis of Robotic Intracardiac Catheter

The disturbances caused by the blood flow and tissue surface motions are major concerns during the motion planning of a intracardiac robotic catheter. Maintaining a stable and safe contact on the desired ablation point is essential for achieving effective lesions during the ablation procedure. In this paper, a probabilistic formulation of the contact stability and the contact safety for intravascular cardiac catheters under the blood flow and surface motion disturbances is presented. Probabilistic contact stability and contact safety metrics, employing a sample based representation of the blood flow velocity distribution and the heart motion trajectory, are introduced. Finally, the contact stability and safety for a MRI-actuated robotic catheter under main pulmonary artery blood flow disturbances and left ventricle surface motion disturbances are analyzed in simulation as example scenarios.

Contact Stability and Contact Safety of a Magnetic Resonance Imaging-Guided Robotic Catheter Under Heart Surface Motion

Contact force quality is one of the most critical factors for safe and effective lesion formation during catheter based atrial fibrillation ablation procedures. In this paper, the contact stability and contact safety of a novel magnetic resonance imaging (MRI)-actuated robotic cardiac ablation catheter subject to surface motion disturbances are studied. First, a quasi-static contact force optimization algorithm, which calculates the actuation needed to achieve a desired contact force at an instantaneous tissue surface configuration is introduced. This algorithm is then generalized using a least-squares formulation to optimize the contact stability and safety over a prediction horizon for a given estimated heart motion trajectory. Four contact force control schemes are proposed based on these algorithms. The first proposed force control scheme employs instantaneous heart position feedback. The second control scheme applies a constant actuation level using a quasi-periodic heart motion prediction. The third and the last contact force control schemes employ a generalized adaptive filter-based heart motion prediction, where the former uses the predicted instantaneous position feedback, and the latter is a receding horizon controller. The performance of the proposed control schemes is compared and evaluated in a simulation environment.

Study on the Stability of the Electrical Connection of High-Temperature Pressure Sensor Based on the Piezoresistive Effect of P-Type SiC

In this study, a preparation method for the high-temperature pressure sensor based on the piezoresistive effect of p-type SiC is presented. The varistor with a positive trapezoidal shape was designed and etched innovatively to improve the contact stability between the metal and SiC varistor. Additionally, the excellent ohmic contact was formed by annealing at 950 °C between Ni/Al/Ni/Au and p-type SiC with a doping concentration of 1018cm−3. The aging sensor was tested for varistors in the air of 25 °C–600 °C. The resistance value of the varistors initially decreased and then increased with the increase of temperature and reached the minimum at ~450 °C. It could be calculated that the varistors at ~100 °C exhibited the maximum temperature coefficient of resistance (TCR) of ~−0.35%/°C. The above results indicated that the sensor had a stable electrical connection in the air environment of ≤600 °C. Finally, the encapsulated sensor was subjected to pressure/depressure tests at room temperature. The test results revealed that the sensor output sensitivity was approximately 1.09 mV/V/bar, which is better than other SiC pressure sensors. This study has a great significance for the test of mechanical parameters under the extreme environment of 600 °C.

The Current-Carrying Tribological Properties of Cu/Graphene Composites

Excellent current-carrying tribological properties including the low-friction, high anti-wear, high current-carrying efficiency, and stability are important for the current-carrying application in transmitting electrical signals and power. Here, the Cu/graphene composites with graphene uniformly distributed in Cu matrix were successfully prepared by combining the electroless plating process and powder metallurgy process. The current-carrying tribological properties including friction, wear, and electrical stability of the Cu/graphene composites with brass pairs were investigated by varying normal applied load and sliding speed under multiple applied voltages. The friction reduction and anti-wear properties of Cu/graphene composites were enhanced by the introduction of graphene. The friction coefficient of the Cu/graphene composites keeps stable under current-carrying and non-current-carrying conditions due to the benefit of the graphene enhancement to Cu. The graphene on wear surface reduces friction force and wear. The current-carrying efficiency and stability increased with the increase of applied load but decreased with increasing sliding speed. The contact stability increased with applied load, while high sliding speed caused the drastic vibration of sliding contact. The studies can provide a beneficial guideline for the current-carrying applications of Cu/graphene composites to reduce the friction and wear.

First pass isolation predicts clinical success after contact force guided paroxysmal atrial fibrillation ablation

Background Contact force (CF) ablation of AF with a focus on catheter-tissue contact stability optimizes clinical success and may help the operator to achieve pulmonary vein (PV) isolation in a single encirclement. While it seems evident that first pass isolation reduces procedure time, the effect on long term clinical success has not been reported. Purpose To evaluate the relationship between first pass isolation and freedom from atrial tachyarrhythmia recurrence at 1 year after PAF ablation. Methods Consecutive de novo PAF ablations were performed with a porous tip contact force catheter in 2017. All ablations used wide-area circumferential ablation and first pass isolation was captured separately for the left and right PVs. CF was held between 10–20 g and the catheter was moved every 10–20 s. RF energy was set at 40W throughout the atrium. Clinical success was defined as freedom from recurrent atrial tachyarrhythmia through 1 year following a 90-day blanking period and freedom from reablation at any time through 1 year. Results The population included 157 patients, age 62.7±11.5, 54.8% male, with mean CHA2DS2-VASc score of 2.3±1.5. Mean procedure times were 76.2±29.8 minutes and 89.2% of the ablations were performed with no fluoroscopy. The overall clinical success rate at 1 year was 86.1%. The number of ipsilateral PV pairs that could be isolated in a single pass was significantly associated with 1-year success (p=0.0043). Achieving first pass isolation on even one ipsilateral PV pair vs. neither pair was significantly associated with clinical success (Table). Conclusion In a real-world setting, first pass isolation on at least one PV side was predictive of 1 year clinical success in a PAF population ablated with CF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Biosense Webster, Inc.